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T follicular regulatory cells
Author(s) -
Sage Peter T.,
Sharpe Arlene H.
Publication year - 2016
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12411
Subject(s) - germinal center , affinity maturation , biology , plasma cell , immunology , b cell , antibody , microbiology and biotechnology , immune system , autoimmunity , immunoglobulin class switching , follicular dendritic cells , cellular differentiation , t cell , antigen presenting cell , genetics , gene
Summary Pathogen exposure elicits production of high‐affinity antibodies stimulated by T follicular helper (Tfh) cells in the germinal center reaction. Tfh cells provide both costimulation and stimulatory cytokines to B cells to facilitate affinity maturation, class switch recombination, and plasma cell differentiation within the germinal center. Under normal circumstances, the germinal center reaction results in antibodies that precisely target foreign pathogens while limiting autoimmunity and excessive inflammation. In order to have this degree of control, the immune system ensures Tfh‐mediated B‐cell help is regulated locally in the germinal center. The recently identified T follicular regulatory (Tfr) cell subset can migrate to the germinal center and inhibit Tfh‐mediated B‐cell activation and antibody production. Although many aspects of Tfr cell biology are still unclear, recent data have begun to delineate the specialized roles of Tfr cells in controlling the germinal center reaction. Here we discuss the current understanding of Tfr‐cell differentiation and function and how this knowledge is providing new insights into the dynamic regulation of germinal centers, and suggesting more efficacious vaccine strategies and ways to treat antibody‐mediated diseases.