Roles for CD22 in regulating the germinal center 4572

Description Humoral immunity generates protective antibodies. The selection of germinal center (GC) B cells is key to generating high-affinity antibodies in the GC. Interactions between GC B cells and follicular helper T (TfH) cells are crucial for guiding B cell differentiation and determining their fate. The regulation of the strength of GC B cell-TfH cell requires further exploration to clarify how these signals drive the formation of memory B cells and plasma cells. CD22, an inhibitory receptor expressed primarily on B cells, plays a significant role in modulating B cell activation. We have established an intrinsic role of CD22 on GC B cells, but ongoing work in our laboratory suggests an extrinsic role of CD22 on GC B cells in regulating the GC. We hypothesize that CD22 modulates B-T cell interactions within the GC through interactions between CD22 and CD22 ligands (CD22L) on TfH cells. To test this hypothesis, we developed models to manipulate the expression of CD22 on GC B cells, CD22L on GC B cells, or CD22L on TfH cells. We will present numerous lines of evidence demonstrating that B-T cell interactions are modulated by CD22-CD22L interaction, which impacts GC output and, in particular, memory B cell formation. Moreover, our results also suggest that natural heterogeneity within CD22L levels on GC B cells regulates the ability of CD22 to bind in trans to TfH cells and, hence, the strength of B-T cells interactions within the GC.