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Nat Immunol. 2009 Apr;10(4):385-93. doi: 10.1038/ni.1715. Epub 2009 Mar 1.

Cytokine-secreting follicular T cells shape the antibody repertoire.

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Howard Hughes Medical Institute and Departments of Medicine and Microbiology & Immunology, University of California San Francisco, USA.


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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