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.

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Publication Details

Journal
Science Advances
Published
2024-11-15
DOI
https://doi.org/10.1126/sciadv.adp1747
Citations
2
Primary Topic
T-cell and B-cell Immunology
Type
article
Field-Weighted Citation Impact
0.48

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article

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

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2 citations
Science Advances
T-cell and B-cell Immunology
0.48
article

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

Ursula Holder, Jessica A. Hamerman, Baidong Hou, Mridu Acharya, Sara Sagadiev, Lucy Z. Li, Jonathan Lagos, Chandrashekhar Pasare, Andrea Montiel-Armendariz
article en
2 citations

Abstract

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.

Science AdvancesVol. 10(46)
Cincinnati Children's Hospital Medical Center (US), Chinese Academy of Sciences (CN), University of Washington (US), Institute of Biophysics (CN), Benaroya Research Institute, University of Cincinnati Medical Center (US)
Cincinnati Children's Hospital Medical Center, National Institutes of Health
Openalex Percentile: Top 34%
T-cell and B-cell Immunology
0.48
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