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

Autor:	Lagos J; Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA., Holder U; Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA., Sagadiev S; Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA., Montiel-Armendariz A; Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA., Li LZ; Center for Fundamental Immunology, Benaroya Research Institute, Seattle, WA, USA.; Molecular and Cellular Biology Program, University of Washington, Seattle, WA, USA., Pasare C; Division of Immunobiology and Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH, USA., Hou B; Institute of Biophysics, Chinese Academy of Sciences, Beijing, China., Hamerman JA; Center for Fundamental Immunology, Benaroya Research Institute, Seattle, WA, USA.; Department of Immunology, University of Washington, Seattle, WA, USA., Acharya M; Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA.; Department of Pediatrics, University of Washington, Seattle, WA, USA.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2024 Nov 15; Vol. 10 (46), pp. eadp1747. Date of Electronic Publication: 2024 Nov 15.
DOI:	10.1126/sciadv.adp1747
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu