Journal
IMMUNOLOGICAL REVIEWS
Volume 247, Issue -, Pages 160-171Publisher
WILEY
DOI: 10.1111/j.1600-065X.2012.01122.x
Keywords
extrafollicular foci; follicular helper T cells; germinal centers; human; lupus
Categories
Funding
- NIH [R01 AR40072, R01 AR44076, P30 AR053495, F31AI081516]
- Rheuminations, Inc.
- Alliance for Lupus Research
- Arthritis Foundation
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Follicular helper T (Tfh) cells play an essential role in helping B cells generate antibodies upon pathogen encounters. Such T-cell help classically occurs in germinal centers (GCs) located in B-cell follicles of secondary lymphoid organs, a site of immunoglobulin affinity maturation and isotype switching. B-cell maturation also occurs extrafollicularly, in the red pulp of the spleen and medullary cords in lymph nodes, with plasma cell formation and antibody production. Development of extrafollicular foci (EF) in T-cell-dependent (TD) immune responses is reliant upon CD4+ T cells with characteristics of Tfh cells. Pathogenic autoantibodies, arising from self-reactive B cells having undergone somatic hypermutation with affinity selection and class switching within GCs and EF, are major contributors to the end-organ injury in systemic autoimmunity. B cells maturing to produce autoantibodies in systemic autoimmune diseases, like those in normal immune responses, largely require T-helper cells. This review highlights Tfh cell development as an introduction to a more in-depth discussion of human Tfh cells and blood borne cells with similar features and the role of these cells in promotion of systemic autoimmunity.
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