B cell-specific CD36 knockout limits T-bet? B cell expansion during immune challenge and obesity 2909

Abstract Description In states of chronic inflammation, a subset of B cells highly responsive to nucleic acid antigens and expressing the pro-inflammatory transcription factor T-bet has been shown to accumulate. Depending on the context, these T-bet? B cells can play dual roles, contributing to antiviral defenses or promoting autoreactive antibody production and exacerbating obesity and metabolic disease. Recent work from our laboratory and others has identified an unusually high expression of the class B scavenger receptor and fatty acid translocase CD36 on T-bet? B cells isolated from both human and murine tissues. Given that CD36 expression in B cells is generally restricted to specific subsets, its presence on these T-bet? B cells suggest a novel role in promoting pathogenic B cell responses. Here, we report that TLR7 agonism enhances the expression of both T-bet and CD36, leading to increased intracellular lipid accumulation in B cells. Furthermore, genetic deletion of CD36 in B cells significantly reduces the expansion of CD11c? T-bet? B cells following both R848 immunization and high-fat diet (HFD) feeding. These findings indicate a critical role for CD36 in the metabolic and immunological regulation of T-bet? B cells, potentially linking lipid metabolism to the differentiation and/or survival of this proinflammatory B cell subset. Funding Sources A.P. is funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health, T34GM149455. G.S.N. is funded by the Biaggini Research Scholars Program at St. Mary’s University. E.A.L. is funded by National Institutes of Health grant R01 AI32789-01A1. B.T.E. is funded by National Institutes of Health grant K12 GM111726. Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)