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

• DOI: 10.1016/j.celrep.2020.01.032
• Publication Date: 2020-02-11T15:55:39Z
• Authors: Adi Biram; Eitan Winter; Alice E. Denton; Irina Zaretsky; Bareket Dassa; Mats Bemark; Michelle A. Linte...; Gur Yaari; Ziv Shulman
• Keywords: 0301 basic medicine; 570; QH301-705.5; 610; 0601 Biochemistry and Cell Biology; plasma cells; Article; Mice; Peyer's Patches; 03 medical and health sciences; antibody; Animals; Signaling Lymphocytic Activation Molecule Associated Protein; Biology (General); B cells; B-Lymphocytes; Germinal Center; 3. Good health; clonal diversification; germinal center; 1116 Medical Physiology; T follicular helper cells; Peyer’s patches; SAP; IgA

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.