Session Time: 4:00pm-5:30pm
Presentation Time: 4:48pm-5:00pm
Location: Room 118-C
Recent studies have defined a crucial role for the B cellactivating 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 subsets that help antibody production in GC. In vivo, various strains of mouce were immunized with keyhole limpet hemocyanin (KLH) emulsified in CFA. BAFF deficiency impairs GC B cell responses to T cell dependent antigens. We first determined that BAFF-/- mice, but not APRIL-/- mice, showed defect on the generation of Tfh cells. BAFF increased the specific antibody production to T celldependent antigens. BAFF might upregulate the Tfh cells via BR3, rather than BCMA or TACI, all of which were receptors of BAFF. With a co-transfer experiment, we further noticed that BAFF is required for the differentiation of Tfh cells and production of GC B cells. In vitro, we induced the differentiation of T cells to Tfh cells with IL-21, IL-6 without TGF-β. And we found that both of BAFF KO or BR3 KO T cells expressed high PD-1 and CXCR5 after 4 days of stimulation, which equaled to the percentage of WT T cells. Those in vitro-differentiated BAFF-/- Tfh-like cells resemble WT Tfh-like cell, which promoted GC responses in BAFF deficient recipient mice after transfusion. Our novel findings support the crucial role of BAFF on the induction of Tfh cell, rather than its function. BAFF and its downstram signaling pathway might be a target for the regulation of autoimmunity disease and chronic graft-versus-host disease.
To cite this abstract in AMA style:Chen M, Li Q, Stohl W, Zheng S, He X, Guo Z. BAFF Binding to T Cell-Expressed BAFF-R Promotes Follicular Helper T Cell Proliferation and GC B Cell Responses [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/baff-binding-to-t-cell-expressed-baff-r-promotes-follicular-helper-t-cell-proliferation-and-gc-b-cell-responses/. Accessed December 12, 2019.
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