Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Faculty of Engineering, Bar Ilan University, Ramat Gan 52900, Israel.
Cell Rep. 2020 Feb 11;30(6):1910-1922.e5. doi: 10.1016/j.celrep.2020.01.032.
Antibodies secreted within the intestinal tract provide protection from the invasion of microbes into the host tissues. Germinal center (GC) formation in lymph nodes and spleen strictly requires SLAM-associated protein (SAP)-mediated T cell functions; however, it is not known whether this mechanism plays a similar role in mucosal-associated lymphoid tissues. Here, we find that in Peyer's patches (PPs), SAP-mediated T cell help is required for promoting B cell selection in GCs, but not for clonal diversification. PPs of SAP-deficient mice host chronic GCs that are absent in T cell-deficient mice. GC B cells in SAP-deficient mice express AID and Bcl6 and generate plasma cells in proportion to the GC size. Single-cell IgA sequencing analysis reveals that these mice host few diversified clones that were subjected to mild selection forces. These findings demonstrate that T cell-derived help to B cells in PPs includes SAP-dependent and SAP-independent functions.
肠道内分泌的抗体可防止微生物侵入宿主组织。淋巴结和脾脏生发中心（GC）的形成严格需要信号淋巴细胞激活分子相关蛋白（SAP）介导的 T 细胞功能；然而，尚不清楚该机制是否在黏膜相关淋巴组织中发挥类似作用。在这里，我们发现在派尔集合淋巴结（PPs）中，SAP 介导的 T 细胞辅助对于促进 GC 中的 B 细胞选择是必需的，但对于克隆多样化则不是必需的。SAP 缺陷型小鼠的 PPs 中存在慢性 GC，而 T 细胞缺陷型小鼠中则不存在。SAP 缺陷型小鼠的 GC B 细胞表达 AID 和 Bcl6，并根据 GC 的大小生成浆细胞。单细胞 IgA 测序分析表明，这些小鼠中存在的受轻度选择压力作用的多样化克隆很少。这些发现表明，PP 中 T 细胞衍生的对 B 细胞的辅助作用包括 SAP 依赖和 SAP 非依赖的功能。
