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B 细胞多样化与 Peyer 斑内慢性生发中心中 SAP 介导的选择力无关。

B Cell Diversification Is Uncoupled from SAP-Mediated Selection Forces in Chronic Germinal Centers within Peyer's Patches.

机构信息

Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.

Faculty of Engineering, Bar Ilan University, Ramat Gan 52900, Israel.

出版信息

Cell Rep. 2020 Feb 11;30(6):1910-1922.e5. doi: 10.1016/j.celrep.2020.01.032.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7016508/a6d9a07174a3/fx1.jpg

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