Bank1 modulates the differentiation and molecular profile of key B cell populations in autoimmunity Gómez Hernández, Gonzalo Toro-Dominguez, Daniel Galicia, Georgina Morell Hita, María Alarcón Riquelme, Marta Eugenia This study aimed at defining the role of the B cell adaptor protein BANK1 in the appearance of ageassociated B cells (ABCs) in 2 SLE mouse models (TLR7.tg6 and imiquimod-induced mice), crossed with Bank1–/– mice. The absence of Bank1 led to a significant reduction in ABC levels, also affecting other B cell populations. To gain deeper insights into their differentiation pathway and the effect of Bank1 on B cell populations, a single-cell transcriptome assay was performed. In the TLR7.tg6 model, we identified 10 clusters within B cells, including an ABC-specific cluster that was decreased in Bank1-deficient mice. In its absence, ABCs exhibited an antiinflammatory gene expression profile, while being proinflammatory in Bank1-sufficient lupus-prone mice. Trajectory analyses revealed that ABCs originated from marginal zone and memory-like B cells, ultimately acquiring transcriptional characteristics associated with atypical memory cells and long-lived plasma cells. Also, Bank1 deficiency normalized the presence of naive B cells, which were nearly absent in lupus-prone mice. Interestingly, Bank1 deficiency significantly reduced a distinct cluster containing IFN-responsive genes. These findings underscore the critical role of Bank1 in ABC development, affecting early B cell stages toward ABC differentiation, and the presence of IFN-stimulated gene– containing B cells, both populations determinant for autoimmunity. 2024-10-28T08:08:09Z 2024-10-28T08:08:09Z 2024-08-20 journal article Gómez Hernández, G. et. al. JCI Insight. 2024;9(19):e179417. [https://doi.org/10.1172/jci. insight.179417] https://hdl.handle.net/10481/96374 10.1172/jci. insight.179417 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional American Society for Clinical Investigation