Cytokine-secreting follicular T cells shape the antibody repertoire

Abstract

High-affinity isotype-switched B cells arise in germinal centers. Locksley and colleagues show that follicular helper T cells are the main cytokine providers for GC B cells and thereby directly influence the ensuing antibody response. High-affinity antibodies are critical for host protection and underlie successful vaccines. The generation of such antibodies requires T cell–dependent help, which mediates germinal center reactions in which mutation and selection of B cells occurs. Using an interleukin 4–reporter system, we show here that CD4+ follicular helper T cells constituted 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. Follicular helper T cells with different cytokine profiles could be isolated as conjugates with B cells undergoing cytokine-specific immunoglobulin class switching with evidence of somatic hypermutation. Our findings support a model in which B cells compete for cytokines produced by follicular helper T cells that shape the affinity and isotype of the antibody response.