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 T-FH 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.