Background/Purpose: BAFF (B cell activating factor belonging to the TNF family) promotes B cells maturation in germinal center. The generation of germinal center depends on T follicular helper cells (Tfh). Overexpression of BAFF and Tfh is found in many autoimmune diseases.  However, whether BAFF has effects on Tfh development is still unclear. In this study, we explored the relationship between BAFF and Tfh in mice.

Methods: Mice were immunized with KLH for 10 days for the induction of Tfh in vivo. Mouse naive CD4+ cells cultured with IL-6 and IL-21 were used for Tfh differentiation in vitro. BAFF^-/-, BAFF transgenic (Tg), April^-/-, BR3^-/-, TACI^-/- and BCMA^-/- mice were used for the mechanism studies. To determine if B cells are required, µMT mice, BCL-2 Tg/µMT and BAFF^-/-/BCL-2 Tg mice were also used. Tfh cells and mature B cell were detected by FACS. Germinal centers were determined by immunofluorescence staining of PNA and IgD. The levels of IgG after KLH immunization were measured by ELISA. The mRNA expression of IL-6and IL-21 was determined by real-time qPCR.

Results:  We showed that BAFF but not April promotes the development of Tfh cells in vivo and in vitro. Furthermore, the development of Tfh cells is dependent upon BR3, but independent on BCMA and TACI. BAFF facilitates the generation of germinal center, and promotes B cells maturation and secretion of IgG. B cells are required for BAFF-promoted Tfh cell formation. We demonstrated that BAFF increases IL-21 mRNA expression in CD4+ T cells, and IL-6 mRNA expression in B cells and dendritic cells.

Conclusion: In summary, these findings provide evidence that BAFF promotes Tfh development, germinal center generation and pathogenesis of autoimmune diseases.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/baff-promotes-t-follicular-helper-cell-development-and-germinal-center-generation-in-mice/