Laboratory of Molecular Oncology, Institut de recherches cliniques de Montréal, Montréal, Québec, Canada.
Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Exp Med. 2021 Mar 1;218(3). doi: 10.1084/jem.20200756.
Expression of the signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is critical for the germinal center (GC) reaction and T cell-dependent antibody production. However, when SAP is expressed normally, the role of the associated SLAM family receptors (SFRs) in these processes is nebulous. Herein, we established that in the presence of SAP, SFRs suppressed the expansion of the GC reaction but facilitated the generation of antigen-specific B cells and antibodies. SFRs favored the generation of antigen-reactive B cells and antibodies by boosting expression of pro-survival effectors, such as the B cell antigen receptor (BCR) and Bcl-2, in activated GC B cells. The effects of SFRs on the GC reaction and T cell-dependent antibody production necessitated expression of multiple SFRs, both in T cells and in B cells. Hence, while in the presence of SAP, SFRs inhibit the GC reaction, they are critical for the induction of T cell-mediated humoral immunity by enhancing expression of pro-survival effectors in GC B cells.
信号淋巴细胞激活分子（SLAM）相关蛋白（SAP）的表达对于生发中心（GC）反应和 T 细胞依赖性抗体产生至关重要。然而，当 SAP 正常表达时，相关 SLAM 家族受体（SFR）在这些过程中的作用尚不清楚。在此，我们发现，在 SAP 的存在下，SFR 抑制了 GC 反应的扩增，但促进了抗原特异性 B 细胞和抗体的产生。SFR 通过增强激活的 GC B 细胞中存活效应物（如 B 细胞抗原受体（BCR）和 Bcl-2）的表达，促进了抗原反应性 B 细胞和抗体的产生。SFR 对 GC 反应和 T 细胞依赖性抗体产生的影响需要在 T 细胞和 B 细胞中表达多种 SFR。因此，虽然 SAP 的存在抑制了 GC 反应，但 SFR 通过增强 GC B 细胞中存活效应物的表达，对于诱导 T 细胞介导的体液免疫至关重要。
