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Final Program


Final Program

Basic Science of Immunology - Adaptive Immunity

W154 - A Multiomics Resource of B Cell Activation Helps Decipher Disease Pathogenesis

Wednesday, June 25, 2025
7:30am - 7:30pm East Coast USA Time
Abstract Text: 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 26 healthy female donors. We stimulated B cells in vitro by targeting key pathways in six activation conditions such as the CD40, BCR, TLR7, TLR9, and a cocktail that promotes differentiation into double negative 2 (DN2) IgD- CD27- CD11c+ 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 genetic risk of IMDs and elucidate IMD genetic risk variants with previously unknown 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.