B cell antigen presentation in the initiation of follicular helper T cell and germinal center differentiation.

High-affinity class-switched Abs and memory B cells are products of the germinal center (GC). The CD4+ T cell help required for the development and maintenance of the GC is delivered by follicular Th cells (T(FH)), a CD4+ Th cell subset characterized by expression of Bcl-6 and secretion of IL-21. The cellular interactions that mediate differentiation of TFH and GC B cells remain an important area of investigation. We previously showed that MHC class II (MHCII)-dependent dendritic cell Ag presentation is sufficient for the differentiation of a T(FH) intermediate (termed pre-T(FH)), characterized by Bcl-6 expression but lacking IL-21 secretion. In this article, we examine the contributions of MHCII Ag presentation by B cells to T(FH) differentiation and GC responses in several contexts. B cells alone do not efficiently prime naive CD4+ T cells or induce T(FH) after protein immunization; however, during lymphocytic choriomeningitis virus infection, B cells induce T(FH) differentiation despite the lack of effector CD4+ T cell generation. Still, MHCII+ dendritic cells and B cells cooperate for optimal T(FH) and GC B cell differentiation in response to both model Ags and viral infection. This study highlights the roles for B cells in both CD4+ T cell priming and T(FH) differentiation, and demonstrates that different APC subsets work in tandem to mediate the GC response.