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Cytokine-secreting follicular T cells shape the antibody repertoire
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Journal Article
Cytokine-secreting follicular T cells shape the antibody repertoire
2009
Overview
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Antigen Presentation - immunology
/ Biomedical and Life Sciences
/ Germinal Center - immunology
/ Immunoglobulin Class Switching
/ Interleukin-4 - biosynthesis
/ Leishmania major - immunology
/ Leishmaniasis, Cutaneous - immunology
/ Lymphocyte Activation - immunology
/ Mice
/ Mutation
/ Somatic Hypermutation, Immunoglobulin
/ T cells
/ T-Lymphocytes, Helper-Inducer - immunology
/ Vaccines
