Immunity
Volume 38, Issue 3, 21 March 2013, Pages 596-605
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Article
Persistent Antigen and Germinal Center B Cells Sustain T Follicular Helper Cell Responses and Phenotype

https://doi.org/10.1016/j.immuni.2012.11.020Get rights and content
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Summary

T follicular helper (Tfh) cells provide help to B cells and are crucial for establishment of germinal center (GC) reactions, including production of high-affinity antibodies and generation of memory B cells and long-lived plasma cells. Here we report that the magnitude of the Tfh cell response was dictated by the amount of antigen and directly correlated with the magnitude of the GC B cell response. In addition, maintenance of the Tfh cell phenotype required sustained antigenic stimulation by GC B cells. In lymphopenic conditions, a strong and prolonged Tfh cell response led to bystander B cell activation, hypergammaglobulinemia, and production of poly- and self-reactive antibodies. These data demonstrate that antigen dose determines the size and duration of the Tfh cell response and GC reaction, highlight the transient nature of the Tfh cell phenotype, and suggest a link between overstimulation of Tfh cells and the development of dysregulated humoral immune responses.

Highlights

► The amount of antigen dictates the Tfh cell and germinal center B cell response ► Tfh cell and germinal center B cell numbers are highly interrelated ► Maintenance of Tfh cells requires persistent antigen and germinal center B cells ► Overstimulation of Tfh cells results in dysregulated antibody responses

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Present address: Howard Hughes Medical Institute and Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA 94143, USA