Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway; K.G. Jebsen Center for B Cell Malignancies, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway; K.G. Jebsen Center for Influenza Vaccine Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Cell Rep. 2021 Aug 10;36(6):109525. doi: 10.1016/j.celrep.2021.109525.
Humoral immunity relies on the efficient differentiation of memory B cells (MBCs) into antibody-secreting cells (ASCs). T helper (Th) signals upregulate B cell receptor (BCR) signaling by potentiating Src family kinases through increasing CD45 phosphatase activity (CD45 PA). In this study, we show that high CD45 PA in MBCs enhances BCR signaling and is essential for their effective ASC differentiation. Mechanistically, Th signals upregulate CD45 PA through intensifying the surface binding of a CD45 ligand, Galectin-1. CD45 PA works as a sensor of T cell help and defines high-affinity germinal center (GC) plasma cell (PC) precursors characterized by IRF4 expression in vivo. Increasing T cell help in vitro results in an incremental CD45 PA increase and enhances ASC differentiation by facilitating effective induction of the transcription factors IRF4 and BLIMP1. This study connects Th signals with BCR signaling through Galectin-1-dependent regulation of CD45 PA and provides a mechanism for efficient ASC differentiation of MBCs.
体液免疫依赖于记忆 B 细胞 (MBC) 高效分化为分泌抗体的细胞 (ASC)。辅助性 T 细胞 (Th) 信号通过增加 Src 家族激酶的活性来增强 B 细胞受体 (BCR) 信号，从而增加 CD45 磷酸酶活性 (CD45PA)。在这项研究中，我们表明 MBC 中高 CD45PA 增强了 BCR 信号，这对于它们的有效 ASC 分化是必不可少的。从机制上讲，Th 信号通过增强 CD45 配体半乳糖凝集素-1 的表面结合来上调 CD45PA。CD45PA 作为 T 细胞辅助的传感器，通过在体内表达干扰素调节因子 4 (IRF4) 来定义高亲和力生发中心 (GC) 浆细胞 (PC) 前体。体外增加 T 细胞辅助会导致 CD45PA 逐渐增加，并通过促进转录因子 IRF4 和 BLIMP1 的有效诱导来增强 ASC 分化。这项研究通过半乳糖凝集素-1 依赖的 CD45PA 调节将 Th 信号与 BCR 信号联系起来，并为 MBC 的有效 ASC 分化提供了一种机制。
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