Aaron M Rosenfeld

Aaron M Rosenfeld

University of Pennsylvania

H-index: 21

North America-United States

About Aaron M Rosenfeld

Aaron M Rosenfeld, With an exceptional h-index of 21 and a recent h-index of 20 (since 2020), a distinguished researcher at University of Pennsylvania,

His recent articles reflect a diverse array of research interests and contributions to the field:

Induction of bronchus-associated lymphoid tissue is an early life adaptation for promoting human B cell immunity

STAT3 signaling in B cells controls germinal center zone organization and recycling

Transcriptome and unique cytokine microenvironment of Castleman disease

A CD45RO+ stem cell memory T cell population intermediate to canonical stem cell memory and central memory T cells in human cancer.

1024 Illuminating stem memory T cell (Tscm) heterogeneity in human cancer: characterization of a unique CD45RO+ Tscm population in human ovarian cancer

Diversification and shared features of tumor‐binding antibody repertoires in tumor, sentinel lymph node and blood of three patients with breast cancer

Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses (vol 54, pg 2877, 2021)

Adaptive Immune Receptor Repertoire (AIRR) Community Guide to TR and IGImmunoglobulin (IG)T cell receptor (TR)Gene annotation Gene Annotation

Aaron M Rosenfeld Information

University

University of Pennsylvania

Position

___

Citations(all)

3549

Citations(since 2020)

3297

Cited By

725

hIndex(all)

21

hIndex(since 2020)

20

i10Index(all)

26

i10Index(since 2020)

25

Email

University Profile Page

University of Pennsylvania

Top articles of Aaron M Rosenfeld

Induction of bronchus-associated lymphoid tissue is an early life adaptation for promoting human B cell immunity

Authors

Rei Matsumoto,Joshua Gray,Ksenia Rybkina,Hanna Oppenheimer,Lior Levy,Lilach M Friedman,Muhammad Khamaisi,Wenzhao Meng,Aaron M Rosenfeld,Rebecca S Guyer,Marissa C Bradley,David Chen,Mark A Atkinson,Todd M Brusko,Maigan Brusko,Thomas J Connors,Eline T Luning Prak,Uri Hershberg,Peter A Sims,Tomer Hertz,Donna L Farber

Journal

Nature Immunology

Published Date

2023/8

Infants and young children are more susceptible to common respiratory pathogens than adults but can fare better against novel pathogens like severe acute respiratory syndrome coronavirus 2. The mechanisms by which infants and young children mount effective immune responses to respiratory pathogens are unknown. Through investigation of lungs and lung-associated lymph nodes from infant and pediatric organ donors aged 0–13 years, we show that bronchus-associated lymphoid tissue (BALT), containing B cell follicles, CD4+ T cells and functionally active germinal centers, develop during infancy. BALT structures are prevalent around lung airways during the first 3 years of life, and their numbers decline through childhood coincident with the accumulation of memory T cells. Single-cell profiling and repertoire analysis reveals that early life lung B cells undergo differentiation, somatic hypermutation and …

STAT3 signaling in B cells controls germinal center zone organization and recycling

Authors

Adam J Fike,Sathi Babu Chodisetti,Nathaniel E Wright,Kristen N Bricker,Phillip P Domeier,Mark Maienschein-Cline,Aaron M Rosenfeld,Sara A Luckenbill,Julia L Weber,Nicholas M Choi,Eline T Luning Prak,Malay Mandal,Marcus R Clark,Ziaur SM Rahman

Journal

Cell reports

Published Date

2023/5/30

Germinal centers (GCs), sites of antibody affinity maturation, are organized into dark (DZ) and light (LZ) zones. Here, we show a B cell-intrinsic role for signal transducer and activator of transcription 3 (STAT3) in GC DZ and LZ organization. Altered zonal organization of STAT3-deficient GCs dampens development of long-lived plasma cells (LL-PCs) but increases memory B cells (MBCs). In an abundant antigenic environment, achieved here by prime-boost immunization, STAT3 is not required for GC initiation, maintenance, or proliferation but is important for sustaining GC zonal organization by regulating GC B cell recycling. Th cell-derived signals drive STAT3 tyrosine 705 and serine 727 phosphorylation in LZ B cells, regulating their recycling into the DZ. RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) analyses identified STAT3 regulated genes that are critical for LZ cell …

Transcriptome and unique cytokine microenvironment of Castleman disease

Authors

Anna Wing,Jason Xu,Wenzhao Meng,Aaron M Rosenfeld,Elizabeth Y Li,Gerald Wertheim,Michele Paessler,Adam Bagg,Dale Frank,Kai Tan,David T Teachey,Megan S Lim,Eline Luning Prak,David C Fajgenbaum,Vinodh Pillai

Journal

Modern Pathology

Published Date

2022/4

Castleman disease (CD) represents a group of rare, heterogeneous and poorly understood disorders that share characteristic histopathological features. Unicentric CD (UCD) typically involves a single enlarged lymph node whereas multicentric CD (MCD) involves multiple lymph node stations. To understand the cellular basis of CD, we undertook a multi-platform analysis using targeted RNA sequencing, RNA in-situ hybridization (ISH), and adaptive immune receptor rearrangements (AIRR) profiling of archived tissue from 26 UCD, 14 MCD, and 31 non-CD reactive controls. UCD showed differential expression and upregulation of follicular dendritic cell markers (CXCL13, clusterin), angiogenesis factors (LPL, DLL4), extracellular matrix remodeling factors (TGFβ, SKIL, LOXL1, IL-1β, ADAM33, CLEC4A), complement components (C3, CR2) and germinal center activation markers (ZDHHC2 and BLK) compared to …

A CD45RO+ stem cell memory T cell population intermediate to canonical stem cell memory and central memory T cells in human cancer.

Authors

Daniel Powell Jr,Monika Eiva,Erica Brown,Veethika Pandey,Alexander Benton,Stacy Thomas,Wenzhao Meng,Aaron Rosenfeld,Eline Luning Prak

Published Date

2022/2/3

T memory stem cells (Tscm) are integral for effective immunotherapy and antitumor responses, but little is known about Tscm immunobiology in solid human tumors. Here we identify self-renewing and multipotent Tscm tumor-infiltrating lymphocytes (TILs) in human cancer and present a novel Tscm subset which expresses CD45RO, is derived from CD45RO-Tscm T cells, and is capable of self-renewal and multipotency. From the analysis of CD45RO+ Tscm differentiation, phenotyping, gene expression, and the broader TCR repertoire, we find CD45RO+ Tscm cells are hierarchically positioned in between canonical CD45RO-Tscm cells and central memory T cells. Notably, CD45RO+ Tscm cells exhibit a gene expression profile with effector capabilities and a tumor-specific phenotype that is more similar to T cells associated with successful immunotherapy than canonical Tscm. Overall, we identify a novel Tscm subset in human cancer which has distinct phenotypic, transcriptional, and effector-like attributes that position it as an attractive subset for future research in the setting of cancer immunotherapy.

1024 Illuminating stem memory T cell (Tscm) heterogeneity in human cancer: characterization of a unique CD45RO+ Tscm population in human ovarian cancer

Authors

Erica Brown,Monika Eiva,Veethika Pandey,Alexander Benton,Stacy Thomas,Wenzhao Meng,Aaron Rosenfeld,Eline Luning Prak,Daniel Powell

Published Date

2022/11/1

Background Stem memory T cells (Tscm) are a unique T cell subset positioned between naïve and central memory (CM) T cells, that express the surface markers CCR7, CD45RA and CD95, and are CD45RO negative.1 Tscm cells can self-renew, are multipotent, and appear to be critical for effective antitumor immunity, but little is known about Tscm immunobiology in human tumors.1-4 Most studies examining canonical Tscm cells are performed using mouse models, expanded tumor-infiltrating lymphocytes (TILs), or peripheral blood T cells, and few studies examine Tscm-like cells directly from human tumors, despite evidence for their crucial role in solid tumor immunotherapeutic treatment.2-6Methods Therefore, we hypothesized that Tscm cells in human ovarian cancer exist and explored Tscm heterogeneity in ovarian cancer tumor digests using flow and mass cytometry. This investigation resulted in the …

Diversification and shared features of tumor‐binding antibody repertoires in tumor, sentinel lymph node and blood of three patients with breast cancer

Authors

Stephanie C Pero,Aaron M Rosenfeld,Girja S Shukla,Linda Mei,Yujing Sun,Wenzhao Meng,David J Fournier,Seth P Harlow,Matthew K Robinson,David N Krag,Eline T Luning Prak,Benjamin C Harman

Journal

Clinical & Translational Immunology

Published Date

2022

Objectives B cell‐mediated immunity can be associated with favorable clinical outcomes in cancer patients. However, the mechanism and features of anti‐tumor immune responses are not well understood. In particular, how B cells expressing tumor‐specific antibodies are distributed (in the tumor vs. the circulation) has not been well defined. Methods We performed an in‐depth analysis of B cell antibody repertoires derived from the tumor, sentinel lymph nodes and peripheral blood of three treatment‐naïve patients with breast cancer. We integrated transcriptional analysis, next‐generation sequencing of immunoglobulin heavy‐chain gene rearrangements and phage display to define B cell responses and clonal architecture in the tumor microenvironment, and to identify antibodies against autologous tumor tissues. Results B cell clonal lineage mapping across sequencing libraries generated from the tumor …

Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses (vol 54, pg 2877, 2021)

Authors

Mohamad-Gabriel Alameh,István Tombácz,Emily Bettini,Katlyn Lederer,Chutamath Sittplangkoon,Joel R Wilmore,Brian T Gaudette,Ousamah Y Soliman,Matthew Pine,Philip Hicks,Tomaz B Manzoni,James J Knox,John L Johnson,Dorottya Laczkó,Hiromi Muramatsu,Benjamin Davis,Wenzhao Meng,Aaron M Rosenfeld,Shirin Strohmeier,Paulo JC Lin,Barbara L Mui,Ying K Tam,Katalin Karikó,Alain Jacquet,Florian Krammer,Paul Bates,Michael P Cancro,Drew Weissman,Eline T Luning Prak,David Allman,Michela Locci,Norbert Pardi

Journal

Immunity

Published Date

2022/6/14

(Immunity 54, 2877–2892. e1–e7, December 14, 2021) Due to an oversight, two authors were omitted from the author list. The author list, the author contribution section, and the acknowledgments have been updated and corrected online and in print. The authors apologize for the error.

Adaptive Immune Receptor Repertoire (AIRR) Community Guide to TR and IGImmunoglobulin (IG)T cell receptor (TR)Gene annotation Gene Annotation

Authors

Lmar Babrak,Susanna Marquez,Christian E Busse,William D Lees,Enkelejda Miho,Mats Ohlin,Aaron M Rosenfeld,Ulrik Stervbo,Corey T Watson,Chaim A Schramm,AIRR Community

Published Date

2022/5/28

High-throughput sequencing of adaptive immune receptor repertoires (AIRR, ie, IG and TR) has revolutionized the ability to carry out large-scale experiments to study the adaptive immune response. Since the method was first introduced in 2009, AIRR sequencing (AIRR-Seq) has been applied to survey the immune state of individuals, identify antigen-specific or immune-state-associated signatures of immune responses, study the development of the antibody immune response, and guide the development of vaccines and antibody therapies. Recent advancements in the technology include sequencing at the single-cell level and in parallel with gene expression, which allows the introduction of multi-omics approaches to understand in detail the adaptive immune response. Analyzing AIRR-seq data can prove challenging even with high-quality sequencing, in part due to the many steps involved and the need to parameterize each step. In this chapter, we outline key factors to consider when preprocessing raw AIRR-Seq data and annotating the genetic origins of the rearranged receptors. We also highlight a number of common difficulties with common AIRR-seq data processing and provide strategies to address them.

Bulk gDNA sequencing of antibody heavy-chain gene rearrangements for detection and analysis of B-cell clone distribution: A method by the AIRR community

Authors

Aaron M Rosenfeld,Wenzhao Meng,Kalisse I Horne,Elaine C Chen,Davide Bagnara,Ulrik Stervbo,Eline T Luning Prak,AIRR Community

Published Date

2022/5/28

In this method we illustrate how to amplify, sequence, and analyze antibody/immunoglobulin (IG) heavychain gene rearrangements from genomic DNA that is derived from bulk populations of cells by nextgeneration sequencing (NGS). We focus on human source material and illustrate how bulk gDNA-based sequencing can be used to examine clonal architecture and networks in different samples that are sequenced from the same individual. Although bulk gDNA-based sequencing can be performed on both IG heavy (IGH) or kappa/lambda light (IGK/IGL) chains, we focus here on IGH gene rearrangements because IG heavy chains are more diverse, tend to harbor higher levels of somatic hypermutations (SHM), and are more reliable for clone identification and tracking. We also provide a procedure, including code, and detailed instructions for processing and annotation of the NGS data. From these data we show how to identify expanded clones, visualize the overall clonal landscape, and track clonal lineages in different samples from the same individual. This method has a broad range of applications, including the identification and monitoring of expanded clones, the analysis of blood and tissue-based clonal networks, and the study of immune responses including clonal evolution.

mRNA Vaccination Induces Durable Immune Memory to SARS-CoV-2 with Continued Evolution to Variants of Concern (preprint)

Authors

Rishi R Goel,Mark M Painter,Sokratis A Apostolidis,Divij Mathew,Wenzhao Meng,Aaron M Rosenfeld,Kendall A Lundgreen,Arnold Reynaldi,David S Khoury,Ajinkya Pattekar,Sigrid Gouma,Leticia Kuri-Cervantes,Philip Hicks,Sarah Dysinger,Amanda Hicks,Harsh Sharma,Sarah Herring,Scott Korte,Amy E Baxter,Derek A Oldridge,Josephine R Giles,Madison E Weirick,Christopher M McAllister,Moses Awofolaju,Nicole Tanenbaum,Elizabeth M Drapeau,Jeanette Dougherty,Sherea Long,Jacob T Hamilton,Maura McLaughlin,Justine C Williams,Sharon Adamski,Oliva Kuthuru,Ian Frank,Michael R Betts,Alba Grifoni,Daniela Weiskopf,Alessandro Sette,Scott E Hensley,Miles P Davenport,Paul Bates,Eline T Luning Prak,Allison R Greenplate,E John Wherry

Published Date

2021

SARS-CoV-2 mRNA vaccines have shown remarkable efficacy, especially in preventing severe illness and hospitalization. However, the emergence of several variants of concern and reports of declining antibody levels have raised uncertainty about the durability of immune memory following vaccination. In this study, we longitudinally profiled both antibody and cellular immune responses in SARS-CoV-2 naive and recovered individuals from pre-vaccine baseline to 6 months post-mRNA vaccination. Antibody and neutralizing titers decayed from peak levels but remained detectable in all subjects at 6 months post-vaccination. Functional memory B cell responses, including those specific for the receptor binding domain (RBD) of the Alpha (B. 1.1. 7), Beta (B. 1.351), and Delta (B. 1.617. 2) variants, were also efficiently generated by mRNA vaccination and continued to increase in frequency between 3 and 6 months post-vaccination. Notably, most memory B cells induced by mRNA vaccines were capable of cross-binding variants of concern, and B cell receptor sequencing revealed significantly more hypermutation in these RBD variant-binding clones compared to clones that exclusively bound wild-type RBD. Moreover, the percent of variant cross-binding memory B cells was higher in vaccinees than individuals who recovered from mild COVID-19. mRNA vaccination also generated antigen-specific CD8+ T cells and durable memory CD4+ T cells in most individuals, with early CD4+ T cell responses correlating with humoral immunity at later timepoints. These findings demonstrate robust, multi-component humoral and cellular immune memory to …

IgV somatic mutation of human anti–SARS-CoV-2 monoclonal antibodies governs neutralization and breadth of reactivity

Authors

Mayara Garcia de Mattos Barbosa,Hui Liu,Daniel Huynh,Greg Shelley,Evan T Keller,Brian T Emmer,Emily Sherman,David Ginsburg,Andrew A Kennedy,Andrew W Tai,Christiane Wobus,Carmen Mirabeli,Thomas M Lanigan,Milagros Samaniego,Wenzhao Meng,Aaron M Rosenfeld,Eline T Luning Prak,Jeffrey L Platt,Marilia Cascalho

Journal

JCI insight

Published Date

2021/5/10

Abs that neutralize SARS-CoV-2 are thought to provide the most immediate and effective treatment for those severely afflicted by this virus. Because coronavirus potentially diversifies by mutation, broadly neutralizing Abs are especially sought. Here, we report a possibly novel approach to rapid generation of potent broadly neutralizing human anti–SARS-CoV-2 Abs. We isolated SARS-CoV-2 spike protein–specific memory B cells by panning from the blood of convalescent subjects after infection with SARS-CoV-2 and sequenced and expressed Ig genes from individual B cells as human mAbs. All of 43 human mAbs generated in this way neutralized SARS-CoV-2. Eighteen of the forty-three human mAbs exhibited half-maximal inhibitory concentrations (IC 50) of 6.7× 10–12 M to 6.7× 10–15 M for spike-pseudotyped virus. Seven of the human mAbs also neutralized (with IC 50< 6.7× 10–12 M) viruses pseudotyped …

mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern

Authors

Rishi R Goel,Mark M Painter,Sokratis A Apostolidis,Divij Mathew,Wenzhao Meng,Aaron M Rosenfeld,Kendall A Lundgreen,Arnold Reynaldi,David S Khoury,Ajinkya Pattekar,Sigrid Gouma,Leticia Kuri-Cervantes,Philip Hicks,Sarah Dysinger,Amanda Hicks,Harsh Sharma,Sarah Herring,Scott Korte,Amy E Baxter,Derek A Oldridge,Josephine R Giles,Madison E Weirick,Christopher M McAllister,Moses Awofolaju,Nicole Tanenbaum,Elizabeth M Drapeau,Jeanette Dougherty,Sherea Long,Kurt D’Andrea,Jacob T Hamilton,Maura McLaughlin,Justine C Williams,Sharon Adamski,Oliva Kuthuru,UPenn COVID Processing Unit‡,Ian Frank,Michael R Betts,Laura A Vella,Alba Grifoni,Daniela Weiskopf,Alessandro Sette,Scott E Hensley,Miles P Davenport,Paul Bates,Eline T Luning Prak,Allison R Greenplate,E John Wherry

Journal

Science

Published Date

2021/10/14

INTRODUCTION Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines are highly effective at preventing infection and especially severe disease. However, the emergence of variants of concern (VOCs) and increasing infections in vaccinated individuals have raised questions about the durability of immunity after vaccination. RATIONALE To study immune memory, we longitudinally profiled antigen-specific antibody, memory B cell, and memory T cell responses in 61 individuals receiving mRNA vaccines from baseline to 6 months postvaccination. A subgroup of 16 individuals had recovered from prior SARS-CoV-2 infection, providing insight into boosting preexisting immunity with mRNA vaccines. RESULTS mRNA vaccination induced robust anti-spike, anti–receptor binding domain (RBD), and neutralizing antibodies that remained above prevaccine baseline levels in most individuals …

Lymphohematopoietic graft-versus-host responses promote mixed chimerism in patients receiving intestinal transplantation

Authors

Jianing Fu,Julien Zuber,Brittany Shonts,Aleksandar Obradovic,Zicheng Wang,Kristjana Frangaj,Wenzhao Meng,Aaron M Rosenfeld,Elizabeth E Waffarn,Peter Liou,Sai-ping Lau,Thomas M Savage,Suxiao Yang,Kortney Rogers,Nichole M Danzl,Shilpa Ravella,Prakash Satwani,Alina Iuga,Siu-hong Ho,Adam Griesemer,Yufeng Shen,Eline T Luning Prak,Mercedes Martinez,Tomoaki Kato,Megan Sykes

Journal

The Journal of Clinical Investigation

Published Date

2021/4/21

In humans receiving intestinal transplantation (ITx), long-term multilineage blood chimerism often develops. Donor T cell macrochimerism (≥ 4%) frequently occurs without graft-versus-host disease (GVHD) and is associated with reduced rejection. Here we demonstrate that patients with macrochimerism had high graft-versus-host (GvH) to host-versus-graft (HvG) T cell clonal ratios in their allografts. These GvH clones entered the circulation, where their peak levels were associated with declines in HvG clones early after transplant, suggesting that GvH reactions may contribute to chimerism and control HvG responses without causing GVHD. Consistently, donor-derived T cells, including GvH clones, and CD34+ hematopoietic stem and progenitor cells (HSPCs) were simultaneously detected in the recipients’ BM more than 100 days after transplant. Individual GvH clones appeared in ileal mucosa or PBMCs before …

Long-term outcomes after gene therapy for adenosine deaminase severe combined immune deficiency

Authors

Bryanna Reinhardt,Omar Habib,Kit L Shaw,Elizabeth Garabedian,Denise A Carbonaro-Sarracino,Dayna Terrazas,Beatriz Campo Fernandez,Satiro De Oliveira,Theodore B Moore,Alan K Ikeda,Barbara C Engel,Gregory M Podsakoff,Roger P Hollis,Augustine Fernandes,Connie Jackson,Sally Shupien,Suparna Mishra,Alejandra Davila,Jack Mottahedeh,Andrej Vitomirov,Wenzhao Meng,Aaron M Rosenfeld,Aoife M Roche,Pascha Hokama,Shantan Reddy,John Everett,Xiaoyan Wang,Eline T Luning Prak,Kenneth Cornetta,Michael S Hershfield,Robert Sokolic,Suk See De Ravin,Harry L Malech,Frederic D Bushman,Fabio Candotti,Donald B Kohn

Journal

Blood, The Journal of the American Society of Hematology

Published Date

2021/10/14

Patients lacking functional adenosine deaminase activity have severe combined immunodeficiency (ADA SCID), which can be treated with ADA enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (HSCT), or autologous HSCT with gene-corrected cells (gene therapy [GT]). A cohort of 10 ADA SCID patients, aged 3 months to 15 years, underwent GT in a phase 2 clinical trial between 2009 and 2012. Autologous bone marrow CD34+ cells were transduced ex vivo with the MND (myeloproliferative sarcoma virus, negative control region deleted, dl587rev primer binding site)–ADA gammaretroviral vector (gRV) and infused following busulfan reduced-intensity conditioning. These patients were monitored in a long-term follow-up protocol over 8 to 11 years. Nine of 10 patients have sufficient immune reconstitution to protect against serious infections and have not needed to resume …

Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals after mRNA vaccination

Authors

Rishi R Goel,Sokratis A Apostolidis,Mark M Painter,Divij Mathew,Ajinkya Pattekar,Oliva Kuthuru,Sigrid Gouma,Philip Hicks,Wenzhao Meng,Aaron M Rosenfeld,Sarah Dysinger,Kendall A Lundgreen,Leticia Kuri-Cervantes,Sharon Adamski,Amanda Hicks,Scott Korte,Derek A Oldridge,Amy E Baxter,Josephine R Giles,Madison E Weirick,Christopher M McAllister,Jeanette Dougherty,Sherea Long,Kurt D’Andrea,Jacob T Hamilton,Michael R Betts,Eline T Luning Prak,Paul Bates,Scott E Hensley,Allison R Greenplate,E John Wherry

Journal

Science immunology

Published Date

2021/4/15

mRNA vaccines for SARS-CoV-2 have been authorized for emergency use. Despite their efficacy in clinical trials, data on mRNA vaccine–induced immune responses are mostly limited to serological analyses. Here, we interrogated antibody and antigen-specific memory B cells over time in 33 SARS-CoV-2 naïve and 11 SARS-CoV-2 recovered subjects. SARS-CoV-2 naïve individuals required both vaccine doses for optimal increases in antibodies, particularly for neutralizing titers against the B.1.351 variant. Memory B cells specific for full-length spike protein and the spike receptor binding domain (RBD) were also efficiently primed by mRNA vaccination and detectable in all SARS-CoV-2 naïve subjects after the second vaccine dose, although the memory B cell response declined slightly with age. In SARS-CoV-2 recovered individuals, antibody and memory B cell responses were significantly boosted after the first …

Altered function and differentiation of age-associated B cells contribute to the female bias in lupus mice

Authors

Edd Ricker,Michela Manni,Danny Flores-Castro,Daniel Jenkins,Sanjay Gupta,Juan Rivera-Correa,Wenzhao Meng,Aaron M Rosenfeld,Tania Pannellini,Mahesh Bachu,Yurii Chinenov,Peter K Sculco,Rolf Jessberger,Eline T Luning Prak,Alessandra B Pernis

Journal

Nature communications

Published Date

2021/8/10

Differences in immune responses to viruses and autoimmune diseases such as systemic lupus erythematosus (SLE) can show sexual dimorphism. Age-associated B cells (ABC) are a population of CD11c+T-bet+ B cells critical for antiviral responses and autoimmune disorders. Absence of DEF6 and SWAP-70, two homologous guanine exchange factors, in double-knock-out (DKO) mice leads to a lupus-like syndrome in females marked by accumulation of ABCs. Here we demonstrate that DKO ABCs show sex-specific differences in cell number, upregulation of an ISG signature, and further differentiation. DKO ABCs undergo oligoclonal expansion and differentiate into both CD11c+ and CD11c− effector B cell populations with pathogenic and pro-inflammatory function as demonstrated by BCR sequencing and fate-mapping experiments. Tlr7 duplication in DKO males overrides the sex-bias and further augments the …

TCR+/BCR+ dual-expressing cells and their associated public BCR clonotype are not enriched in type 1 diabetes

Authors

Alberto Sada Japp,Wenzhao Meng,Aaron M Rosenfeld,Daniel J Perry,Puchong Thirawatananond,Rhonda L Bacher,Chengyang Liu,Jay S Gardner,Mark A Atkinson,Klaus H Kaestner,Todd M Brusko,Ali Naji,Eline T Luning Prak,Michael R Betts

Journal

Cell

Published Date

2021/2/4

Ahmed and colleagues recently described a novel hybrid lymphocyte expressing both a B and T cell receptor, termed double expresser (DE) cells. DE cells in blood of type 1 diabetes (T1D) subjects were present at increased numbers and enriched for a public B cell clonotype. Here, we attempted to reproduce these findings. While we could identify DE cells by flow cytometry, we found no association between DE cell frequency and T1D status. We were unable to identify the reported public B cell clone, or any similar clone, in bulk B cells or sorted DE cells from T1D subjects or controls. We also did not observe increased usage of the public clone VH or DH genes in B cells or in sorted DE cells. Taken together, our findings suggest that DE cells and their alleged public clonotype are not enriched in T1D. This Matters Arising paper is in response to Ahmed et al. (2019), published in Cell. See also the response by …

Maintenance of the human memory T cell repertoire by subset and tissue site

Authors

Michelle Miron,Wenzhao Meng,Aaron M Rosenfeld,Shirit Dvorkin,Maya Meimei Li Poon,Nora Lam,Brahma V Kumar,Yoram Louzoun,Eline T Luning Prak,Donna L Farber

Journal

Genome medicine

Published Date

2021/6/14

BackgroundImmune-mediated protection is mediated by T cells expressing pathogen-specific T cell antigen receptors (TCR) that are maintained at diverse sites of infection as tissue-resident memory T cells (TRM) or that disseminate as circulating effector-memory (TEM), central memory (TCM), or terminal effector (TEMRA) subsets in blood and tissues. The relationship between circulating and tissue resident T cell subsets in humans remains elusive, and is important for promoting site-specific protective immunity.MethodsWe analyzed the TCR repertoire of the major memory CD4+ and CD8+T cell subsets (TEM, TCM, TEMRA, and TRM) isolated from blood and/or lymphoid organs (spleen, lymph nodes, bone marrow) and lungs of nine organ donors, and blood of three living individuals spanning five decades of life. High-throughput sequencing of the variable (V) portion of individual TCR genes for each subset …

IgA plasma cells are long-lived residents of gut and bone marrow that express isotype-and tissue-specific gene expression patterns

Authors

Joel R Wilmore,Brian T Gaudette,Daniela Gómez Atria,Rebecca L Rosenthal,Sarah Kim Reiser,Wenzhao Meng,Aaron M Rosenfeld,Eline T Luning Prak,David Allman

Journal

Frontiers in immunology

Published Date

2021/12/24

Antibody secreting plasma cells are made in response to a variety of pathogenic and commensal microbes. While all plasma cells express a core gene transcription program that allows them to secrete large quantities of immunoglobulin, unique transcriptional profiles are linked to plasma cells expressing different antibody isotypes. IgA expressing plasma cells are generally thought of as short-lived in mucosal tissues and they have been understudied in systemic sites like the bone marrow. We find that IgA+ plasma cells in both the small intestine lamina propria and the bone marrow are long-lived and transcriptionally related compared to IgG and IgM expressing bone marrow plasma cells. IgA+ plasma cells show signs of shared clonality between the gut and bone marrow, but they do not recirculate at a significant rate and are found within bone marrow plasma cells niches. These data suggest that systemic and mucosal IgA+ plasma cells are from a common source, but they do not migrate between tissues. However, comparison of the plasma cells from the small intestine lamina propria to the bone marrow demonstrate a tissue specific gene transcription program. Understanding how these tissue specific gene networks are regulated in plasma cells could lead to increased understanding of the induction of mucosal versus systemic antibody responses and improve vaccine design.

Sex-specific differences in the function and differentiation of ABCs mark TLR7-driven immunopathogenesis

Authors

Edd Ricker,Michela Manni,Danny Flores-Castro,Daniel Jenkins,Sanjay Gupta,Juan Rivera-Correa,Wenzhao Meng,Aaron M Rosenfeld,Tania Pannellini,Mahesh Bachu,Yurii Chinenov,Peter K Sculco,Rolf Jessberger,Eline T Luning Prak,Alessandra B Pernis

Journal

bioRxiv

Published Date

2021/1/21

Sex differences characterize immune responses to viruses like SARS-CoV2 and autoimmune diseases like SLE. ABCs are an emerging population of CD11c+ T-bet+ B cells critical for antiviral responses and autoimmune disorders. DEF6 and SWAP70, are two homologous molecules whose combined absence in double-knock-out mice (DKOs) leads to a lupus syndrome in females marked by an accumulation of ABCs. Here we demonstrate that DKO ABCs exhibit sex-specific differences in their expansion, upregulation of an ISG signature, and further differentiation. BCR sequencing and fate mapping experiments reveal that DKO ABCs undergo oligoclonal expansion and differentiate into both CD11c+ and CD11c− effector populations with pathogenic and proinflammatory potential. Tlr7 duplication in DKO males overrides the sex-bias and further augments the dissemination and pathogenicity of ABCs resulting in severe pulmonary inflammation and early mortality. Thus, sexual dimorphism shapes the expansion, function, and differentiation of ABCs contributing to the sex-bias that accompanies TLR7-driven immunopathogenesis.

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The h-index of Aaron M Rosenfeld has been 20 since 2020 and 21 in total.

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The articles with the titles of

Induction of bronchus-associated lymphoid tissue is an early life adaptation for promoting human B cell immunity

STAT3 signaling in B cells controls germinal center zone organization and recycling

Transcriptome and unique cytokine microenvironment of Castleman disease

A CD45RO+ stem cell memory T cell population intermediate to canonical stem cell memory and central memory T cells in human cancer.

1024 Illuminating stem memory T cell (Tscm) heterogeneity in human cancer: characterization of a unique CD45RO+ Tscm population in human ovarian cancer

Diversification and shared features of tumor‐binding antibody repertoires in tumor, sentinel lymph node and blood of three patients with breast cancer

Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses (vol 54, pg 2877, 2021)

Adaptive Immune Receptor Repertoire (AIRR) Community Guide to TR and IGImmunoglobulin (IG)T cell receptor (TR)Gene annotation Gene Annotation

...

are the top articles of Aaron M Rosenfeld at University of Pennsylvania.

What is Aaron M Rosenfeld's total number of citations?

Aaron M Rosenfeld has 3,549 citations in total.

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