Figure 8. Model of Tfh differentiation and maintenance.

(A) Our data suggest that in both immunization and autoimmune mouse models, GC B cells are actively providing signals to maintain optimal Tfh numbers during the course of the GC reaction. In the immunization model, ICOSL:ICOS but not B7.2:CD28 signaling, is required for Tfh maintenance. Interestingly, in the spontaneous autoimmune model both signals are required to maintain optimal numbers of mature Tfh. (B) Previous studies have shown that Tfh differentiation is a multistage process: Dendritic cells initiate the differentiation of naïve T cells into pre-Tfh. Upon upregulation of CXCR5, these pre-Tfh are able to enter the follicle and interact with cognate B cells. This interaction with B cells drives the full polarization of Tfh into mature Tfh which is required for the germinal center reaction. Our data in an immunization model demonstrate that once fully mature, Tfh continue to require signals from GC B cells to sustain their maintenance. We further show that the same B cell dependence continues to play a role in spontaneous models of autoimmunity.