Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA.
Center for Fundamental Immunology, Benaroya Research Institute, Seattle, WA, USA.
Sci Adv. 2024 Nov 15;10(46):eadp1747. doi: 10.1126/sciadv.adp1747.
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.
B 细胞衔接蛋白用于 PI3-激酶（BCAP）是一种与多种免疫受体（包括 B 细胞受体（BCR））信号转导相关的衔接分子。然而，BCAP 在抗体反应中的细胞内作用尚不清楚。我们研究了 BCAP 在 B 细胞对病毒颗粒反应中的作用，发现了一种以前未被识别的机制，BCAP 通过该机制调节抗原特异性反应。在小鼠中特异性敲除 B 细胞中的 BCAP 会导致抗原特异性反应减少，这是由于 BCR 抗原内吞作用缺陷所致。BCAP 对于协调抗原周围肌动蛋白的重排以通过 BCR 进行有效的内吞作用以及抗原的细胞内处理是必需的。因此，B 细胞中 BCAP 的缺失会导致抗原内吞作用缺陷，阻碍抗原衍生信号的传播，并降低 B 细胞向 T 细胞呈递抗原的能力。因此，我们的研究阐明了 BCAP 如何调节 B 细胞对复杂抗原的反应，并阐明了抗原在 B 细胞内的定位决定了不同的 B 细胞激活结果。
