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Abstract
Germinal centers (GC) have been known as key anatomic structures in humoral immunity,
where isotype switching and affinity maturation occur. As a consequence, elucidation
of GC regulation has potential implications for the understanding of autoantibody-mediated
diseases. It is now accepted that different regulatory mechanisms coexist, including
the action of a specialized population of Foxp3+ regulatory T cells with unique access
to the B-cell follicle: the T follicular regulatory (Tfr) cells. Tfr cells develop
through a multistep process requiring migration through different compartments of
lymphoid tissues. This review discusses the ontogeny and physiology of Tfr cells,
their distribution within distinct anatomic compartments, and their function. A greater
understanding of Tfr biology and GC regulation is likely to lead to better stratification
of patients with autoantibody-mediated diseases, and to the identification of novel
therapeutic targets.