B cell adapter for PI 3-kinase (BCAP) coordinates antigen internalization and trafficking through the B cell receptor.

B cell adapter for PI 3-kinase (BCAP) is an adaptor molecule associated with signaling through multiple immune receptors, including the B cell receptor (BCR). However, B cell-intrinsic role of BCAP in antibody responses is unclear. We investigated the role of BCAP in B cell response to viral particles and found a previously unidentified mechanism by which BCAP regulates antigen-specific responses. B cell-specific deletion of BCAP in mice leads to decreases in antigen-specific responses through defects in BCR-antigen endocytosis. BCAP is necessary to orchestrate actin reorganization around the antigen for efficient endocytosis through BCR and intracellular processing of antigens. Therefore, loss of BCAP from B cells leads to defects in antigen endocytosis, hampering the propagation of antigen-derived signals and decreasing the ability of B cells to present antigens to T cells. Thus, our study clarifies how BCAP regulates B cell responses to complex antigens and elucidates that antigen positioning inside B cells determines different B cell activation outcomes.

Citation

Jonathan Lagos, Ursula Holder, Sara Sagadiev, Andrea Montiel-Armendariz, Lucy Z Li, Chandrashekhar Pasare, Baidong Hou, Jessica A Hamerman, Mridu Acharya. B cell adapter for PI 3-kinase (BCAP) coordinates antigen internalization and trafficking through the B cell receptor. Science advances. 2024 Nov 15;10(46):eadp1747

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PMID: 39546610

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