The role of germinal centers in T cell receptor revision (160.10)

Abstract

Abstract CD4+ T cells in Vβ5 transgenic mice become tolerant to an endogenous superantigen through either deletion or T cell receptor (TCR) revision. In the revision process, T cells downregulate surface Vβ5 expression and undergo RAG-mediated rearrangement and expression of endogenous TCRs. Revision occurs in germinal centers (GCs), suggesting that revising T cells may be follicular helper T cells (Tfh). We are studying whether revising T cells have a Tfh phenotype and whether GC interactions are required for revision. Preliminary data indicate that revising T cells have an RNA phenotype closely resembling that of Tfh and distinct from that of post-revision T cells. Studies on the intracellular and surface phenotype of revising and post-revision T cells are ongoing. The importance of GCs to TCR revision is being analyzed using SAP and CXCR5 null mice. SAP is required for prolonged interactions of B and T cells in the GC, and CXCR5 is required for cellular migration into the follicle. Analyses of mixed chimeras generated using CXCR5 null and wildtype bone marrow donors are ongoing. CXCR5 and SAP null mice have reduced numbers of post-revision T cells, but no reduction in revision intermediates. These results suggest that migration into the follicle and prolonged B-T cell interactions are both required for completion, but not initiation, of TCR revision.