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.

中文翻译：

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PI 3-激酶 （BCAP） 的 B 细胞接头通过 B 细胞受体协调抗原内化和运输


PI 3-激酶 B 细胞接头蛋白 （BCAP） 是一种接头蛋白分子，通过多种免疫受体（包括 B 细胞受体 （BCR））与信号转导相关。然而，BCAP 在抗体反应中的 B 细胞内在作用尚不清楚。我们研究了 BCAP 在 B 细胞对病毒颗粒反应中的作用，并发现了 BCAP 调节抗原特异性反应的先前未确定的机制。小鼠 BCAP 的 B 细胞特异性缺失通过 BCR 抗原内吞作用缺陷导致抗原特异性反应降低。BCAP 对于协调抗原周围的肌动蛋白重组以通过 BCR 和抗原的细胞内加工进行有效的内吞作用是必要的。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 细胞将抗原呈递给 T 细胞的能力。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 B 细胞内的抗原定位决定了不同的 B 细胞活化结果。