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.
Authors
- Ursula Holder (ORCID: https://orcid.org/0000-0002-8122-7965)
- Jessica A. Hamerman (ORCID: https://orcid.org/0000-0001-5864-5299)
- Baidong Hou
- Mridu Acharya (ORCID: https://orcid.org/0000-0001-7078-2560)
- Sara Sagadiev (ORCID: https://orcid.org/0000-0002-8371-0977)
- Lucy Z. Li (ORCID: https://orcid.org/0000-0003-4616-736X)
- Jonathan Lagos (ORCID: https://orcid.org/0000-0003-4270-6813)
- Chandrashekhar Pasare (ORCID: https://orcid.org/0000-0002-8142-2488)
- Andrea Montiel-Armendariz
Institutions
- 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)
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
Funders
- Cincinnati Children's Hospital Medical Center
- National Institutes of Health