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

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. [Display omitted] •Chronic germinal centers in Peyer’s patches are formed in SAP-deficient mice•SAP-independent germinal centers arise in response to influenza infection•Few highly diversified clones dominate the SAP-independent germinal centers•Germinal center B cells in SAP-deficient mice are subjected to mild selection forces SAP is required for proper T cell help in germinal centers (GCs). Biram et al. show that SAP-independent GCs are formed within Peyer’s patches. These GCs host highly diversified clones that are subjected to mild selection forces, demonstrating that clonal diversification can be uncoupled from clonal selection in chronic GCs.