Abstract
Immunization leads to the formation of germinal centres (GCs) that contain both T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Whether T-cell receptor (TCR) specificity defines the differential functions of Tfh and Tfr cells is unclear. Here we show that antigen-specific T cells after immunization are preferentially recruited to the GC to become Tfh cells, but not Tfr cells. Tfh cells, but not Tfr cells, also proliferate efficiently on restimulation with the same immunizing antigen in vitro. Ex vivo TCR repertoire analysis shows that immunization induces oligoclonal expansion of Tfh cells. By contrast, the Tfr pool has a TCR repertoire that more closely resembles that of regulatory T (Treg) cells. Our data thus indicate that the GC Tfh and Tfr pools are generated from distinct TCR repertoires, with Tfh cells expressing antigen-responsive TCRs to promote antibody responses, and Tfr cells expressing potentially autoreactive TCRs to suppress autoimmunity.
Highlights
Immunization leads to the formation of germinal centres (GCs) that contain both T follicular helper (Tfh) and T follicular regulatory (Tfr) cells
When OT-II.Rag þ cells were transferred into TCRb À / À mice we found that they readily gave rise to a population of Tfr cells
Given the documented capacity of Tfr cells to prevent autoantibody-mediated autoimmunity[13,14,15,16,17], we investigated the possibility that the T-cell receptor (TCR) usage by Tfh and Tfr populations from the same GCs is different: only the Tfh repertoire is biased towards the immunizing antigens
Summary
Immunization leads to the formation of germinal centres (GCs) that contain both T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Thymus-dependent humoral immune responses are critical for protection against pathogens but are a central protective mechanism of most vaccines These antibody-mediated responses depend on germinal centres (GCs)—anatomical structures inside the B-cell zone—where T follicular helper (Tfh) cells interact with and provide help to B cells, enabling affinity maturation and isotype switching[1]. Protective immune responses are promoted by Tfh cells, which, with a TCR repertoire specific for an immunizing antigen, provide help to B cells and enable BCR affinity maturation, whereas the Tfr cell TCR repertoire, which is predominantly autoreactive, enables these cells to suppress autoreactive affinitymatured B-cell clones, preventing autoantibody-mediated autoimmunity
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