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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We thank G. Kelsoe (Duke University), M. Nussenzweig (Rockefeller University), K. McBride (Rockefeller University) and A. N. McKenzie (Trinity College, Dublin) for reagents and suggestions; J. Cyster, A. DeFranco and C. Allen for review and comments; and N. Flores, L. Stowring and C. McArthur for technical expertise. Supported by the National Institutes of Allergy and Infectious Diseases (AI026918 and AI077439), the Howard Hughes Medical Institute, the Sandler Asthma Basic Research Center of the University of California San Francisco and the Juvenile Diabetes Research Foundation–Irvington Institute (R.L.R.).
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Reinhardt, R., Liang, HE. & Locksley, R. Cytokine-secreting follicular T cells shape the antibody repertoire. Nat Immunol 10, 385–393 (2009). https://doi.org/10.1038/ni.1715
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