@misc{10481/96374, year = {2024}, month = {8}, url = {https://hdl.handle.net/10481/96374}, abstract = {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.}, organization = {Plan Estatal de Investigación Científica, Técnica e Innovación 2013-2016 to MEAR}, organization = {Ministerio de Ciencia e Innovación (PID2020-113776GB-I00 to MEAR)}, organization = {Fondo Europeo de Desarrollo Regional (FEDER)}, organization = {Consejería de Salud y Familias de la Junta de Andalucía (PE0297-2019 to MEAR)}, organization = {Swedish Research Council (2022-01000)}, organization = {Gustaf den Ve-80-års Fond}, publisher = {American Society for Clinical Investigation}, title = {Bank1 modulates the differentiation and molecular profile of key B cell populations in autoimmunity}, doi = {10.1172/jci. insight.179417}, author = {Gómez Hernández, Gonzalo and Toro-Dominguez, Daniel and Galicia, Georgina and Morell Hita, María and Alarcón Riquelme, Marta Eugenia}, }