Abstract
SummaryAntibodies 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.
Highlights
The clearance of invading microbes and the establishment of enduring protection from harmful pathogens depends on B cell differentiation into plasma cells (PCs) that secrete high-affinity antibodies
signaling lymphocyte activation molecule (SLAM)-associated protein (SAP)-Deficient Mice Host Small Germinal center (GC) within Peyer’s patches (PPs) SAP-mediated T cell help is essential for mounting a T celldependent immune response in draining lymph nodes (LNs) and spleen in response to immunization or microbe invasion, but it is not known whether this adaptor protein regulates chronic immune responses in the gut
Close analysis of the LNs from either SAP- or TCRa-deficient immunized mice revealed that tdTomato-expressing B cells were scattered throughout the LN cortex, demonstrating that T cell help is essential for GC formation but not for initial activation-induced cytidine deaminase (AID) expression (Figure 1A)
Summary
The clearance of invading microbes and the establishment of enduring protection from harmful pathogens depends on B cell differentiation into plasma cells (PCs) that secrete high-affinity antibodies These cells are generated in microanatomical sites, known as germinal centers (GCs), which emerge in lymphoid organs primarily in response to vaccination or pathogen invasion (Victora and Nussenzweig, 2012). As opposed to class switch recombination (CSR) of B cells to IgG1 within draining LNs and spleen in response to immunization or microbe invasion, switching to the IgA isotype in PPs can take place in the absence of T cell-derived signals (Bergqvist et al, 2006; Macpherson et al, 2000; Mombaerts et al, 1994) It remains unknown whether other B cell functions in chronic GCs, such as clonal diversification and affinity-based selection, require T cell help
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