Concurrent Oral Sessions

Abstract

Recent studies have defined a crucial role for the B cell-activating factor belonging to TNF family (BAFF) in promoting germinal center (GC) responses in mouse model. BAFF-deficient (BAFF-/-) mouse was defective in primary B cell survival and development, including a loss of transitional type 2, follicular, and marginal zone B cells. This fact prompted us to investigate the influence of BAFF on follicular helper T (Tfh) cells, another important subset that helps antibody production in GC. In vivo, various strains of mice were immunized with keyhole limpet hemocyanin (KLH) emulsified in CFA. We first observed that BAFF deficiency impairs GC B cell responses to T cell dependent antigens. We also found that BAFF-/- mice, but not APRIL-/- mice, have a defect on the generation of Tfh cells and antibody production. Similar to BAFF-/- mice, BR3-/- mice also showed almost none of Tfh cells in draining lymph node. While BCMA-/- or TACI-/- mice appeared to be normal or even higher percentage of Tfh cells in spleen and lymph node after antigen stimulation. Thus, BAFF might upregulate the Tfh cells via BR3, rather than BCMA or TACI, all of which are BAFF receptors. To rule out the influence of impaired B cell by BAFF, Bcl2 Tg and BAFF-/-Bcl2 Tg mice were employed for keeping survival B cells in BAFF deficient background. To the end, we found that lack of BAFF still caused impaired Tfh cell and antibody production. With a co-transfer experiment, we further comfirmed that BAFF is required for the differentiation of Tfh cells and production of GC B cells. In vitro, we demonstrated that BAFF increases IL-21 mRNA expression in CD4+ T cells, and IL-6 mRNA expression in B cells and dendritic cells. In summary, these findings provide evidence that BAFF promotes Tfh development, germinal center generation and pathogenesis of autoimmune diseases.