Cytokine-secreting follicular T cells shape the antibody repertoire

High-affinity antibodies are critical for host protection and underlie successful vaccines. Generation of such antibodies requires T cell-dependent help, which mediates germinal center (GC) reactions where mutation and selection of B cells occurs. Using an interleukin 4 (IL-4)-reporter system, we show that follicular CD4(+) T (T(FH)) cells comprised essentially all of the cytokine-secreting T cells in lymph nodes and were functionally distinct from T cells secreting the same cytokine in peripheral tissues. T(FH) cells with different cytokine profiles could be isolated as conjugates with B cells undergoing cytokine-specific immunoglobulin class-switching with evidence of somatic hypermutation. These findings subport a model wherein B cells compete for cytokines produced by T(FH) cells that shape the affinity and isotype of the antibody response.