Cytokine-secreting follicular T cells shape the antibody repertoire

RL Reinhardt, HE Liang, RM Locksley - Nature immunology, 2009 - nature.com
Nature immunology, 2009nature.com
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 …
Abstract
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.
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