Cytokine-secreting follicular T cells shape the antibody repertoire.
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.
Reinhardt
R Lee
RL
Howard Hughes Medical Institute and Departments of Medicine and Microbiology & Immunology, University of California San Francisco, USA.
Liang
Hong-Erh
HE
Locksley
Richard M
RM
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation; D017951:Antigen Presentation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D017930:Genes, Reporter; D018858:Germinal Center / Q000276:immunology*; D017578:Immunoglobulin Class Switching; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D027041:Somatic Hypermutation, Immunoglobulin; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000906:Antibodies; D015847:Interleukin-4