A multiomics resource of B cell activation helps decipher disease pathogenesis 4355

Abstract Description Most genetic variants that confer risk of complex immune-mediated diseases (IMD) affect gene regulation in specific cell types. Their target genes and focus cell types are often unknown, partially because some effects are hidden in untested cell states. B cells are drivers of IMDs such as lupus and multiple sclerosis. Yet, B cell activation states are underrepresented in functional genomics studies. In this study, we obtained B cells from a total of 23 healthy female donors. We stimulated B cells in vitro by targeting key pathways in six activation conditions such as the CD40, B cell receptor, TLR7, TLR9, and a cocktail that promotes differentiation into double negative 2 (DN2) B cells. We profiled B cell activation at different time points using RNA-seq, single-cell RNA-seq coupled with surface protein markers (CITE-seq), and ATAC-seq. We provide an in-depth characterization of how IMD-associated genes respond to stimuli and group into modules with distinct functions. Using single-cell data, we describe pathway-dependent B cell fates. Chromatin data reveal the transcription factors involved in pathway-dependent B cell activation. These open chromatin regions capture a significant proportion of the heritability of IMDs and elucidate IMD-associated variants with previously unknow function. These data are shared via an interactive browser that can be used to query the dynamics of gene regulation and B cell differentiation during activation by different stimuli. Funding Sources Supported by Lupus Research Alliance (LRA); Arthritis National Research Foundation (ANRF); Gilead; Join Biology Consortium (JBC) Topic Categories Computational and Systems Immunology (COMP)

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Publication Details

Journal
The Journal of Immunology
Published
2025-11-01
DOI
https://doi.org/10.1093/jimmun/vkaf283.2051
Primary Topic
T-cell and B-cell Immunology
Type
article
Field-Weighted Citation Impact
0.00
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article

A multiomics resource of B cell activation helps decipher disease pathogenesis 4355

Brian Wauford, Vitor R. C. Aguiar, Vaishali Prahalad, Junning Case et al.
The Journal of Immunology
T-cell and B-cell Immunology
article

A multiomics resource of B cell activation helps decipher disease pathogenesis 4355

Brian Wauford, Vitor R. C. Aguiar, Vaishali Prahalad, Junning Case, Lauren A. Henderson, Mariasilvia Colantuoni, Nada A. Abdelaziz, Jeffrey A. Sparks, Carl D. Langefeld, Roxane Darbousset, Kevin S. Cashman, Scott A. Jenks, Kevin Wei, María Gutiérrez‐Arcelus, Emily Banasiak, Raquel Laza‐Briviesca, Mehdi Benamar, Esra Meidan, Nicolaj Hackert, Henry W. Long, Margaret H. Chang, Peter A. Nigrović, Marc Todd, Miguel Gomez, Pui Y. Lee, Alexandra Wactor, Marcos Chiñas, Igñacio Sanz, Marcella E. Franco, Daniela Fernandez‐Salinas, Qiang Wang, Zhu Zhu, Qian Xiao, Paloma Cejas, Esther C. Zumaquero-Martinez
article en

Abstract

Abstract Description Most genetic variants that confer risk of complex immune-mediated diseases (IMD) affect gene regulation in specific cell types. Their target genes and focus cell types are often unknown, partially because some effects are hidden in untested cell states. B cells are drivers of IMDs such as lupus and multiple sclerosis. Yet, B cell activation states are underrepresented in functional genomics studies. In this study, we obtained B cells from a total of 23 healthy female donors. We stimulated B cells in vitro by targeting key pathways in six activation conditions such as the CD40, B cell receptor, TLR7, TLR9, and a cocktail that promotes differentiation into double negative 2 (DN2) B cells. We profiled B cell activation at different time points using RNA-seq, single-cell RNA-seq coupled with surface protein markers (CITE-seq), and ATAC-seq. We provide an in-depth characterization of how IMD-associated genes respond to stimuli and group into modules with distinct functions. Using single-cell data, we describe pathway-dependent B cell fates. Chromatin data reveal the transcription factors involved in pathway-dependent B cell activation. These open chromatin regions capture a significant proportion of the heritability of IMDs and elucidate IMD-associated variants with previously unknow function. These data are shared via an interactive browser that can be used to query the dynamics of gene regulation and B cell differentiation during activation by different stimuli. Funding Sources Supported by Lupus Research Alliance (LRA); Arthritis National Research Foundation (ANRF); Gilead; Join Biology Consortium (JBC) Topic Categories Computational and Systems Immunology (COMP)

The Journal of ImmunologyVol. 214(Supplement_1)
Broad Institute (US), Brigham and Women's Hospital (US), Boston Children's Hospital (US), Harvard University (US), Emory University (US), Heidelberg University (DE), University Hospital Heidelberg (DE), University of Alabama at Birmingham (US), Dana-Farber Cancer Institute (US), Wake Forest University (US)
Openalex Percentile: Top 62%
T-cell and B-cell Immunology
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