(261) Roles for CD22 in regulating the germinal center

Introduction/Rationale: High-affinity antibody selection in Germinal Centers (GCs) requires complex B cell-TfH interactions. The inhibitory receptor CD22 on B cells binds to sialic acid ligands (CD22L) found on T cells. Given the increased CD22L expression on TfH cells, this study tests the hypothesis that CD22L on follicular T cells critically regulates B-T cell interactions in GCs, thus shaping the humoral immune response.

Methods: To investigate the role of CD22L on T cells in the GC response, a tamoxifen-inducible murine model (S6KO) was used to selectively delete CD22L from CD4+ T cells by knocking out the ST6Gal1 gene. Following immunization with an antigen, the GC response was assessed using three primary methods: Flow cytometry was used to track and quantify various B and T cell populations in the spleen; ELISA measured the concentration and affinity of antigen-specific antibodies in the serum; and Immunofluorescence staining was used to determine the size and total number of GCs in the spleen.

Results: The findings consistently show that the loss of CD22L on CD4+ T cells severely disrupted the GC response and impaired antibody affinity maturation. Specifically, it was confirmed that the CD22/CD22L axis mediates B-T cell interaction. Mice with CD22L-deficient T cells exhibited a significant decrease in key populations, including GC B cells, TfH cells, and TfR cells, and disruption of overall GC formation. Functionally, these mice showed a significant decrease in high-affinity IgG and, notably, developed anti-nucleoprotein autoantibodies.

Conclusion: CD22-CD22L interactions between GC B and Tfh cells are essential for a functional germinal center response and effective humoral immunity. The data confirm that CD22 and CD22L mediate B-T cell interaction strength. Crucially, removing CD22L from CD4+ T cells severely disrupted the GC environment and impaired antibody affinity maturation. This highlights that CD22-CD22L interactions in critical in GC.