1. follicular regulatory T cells control the germinal center response
- Author
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Linterman, Michelle A., Pierson, Wim, Lee, Sau K., Kallies, Axel, Kawamoto, Shimpei, Rayner, Tim F., Srivastava, Monika, Divekar, Devina P., Beaton, Laura, Hogan, Jennifer J., Fagarasan, Sidonia, Liston, Adrian, Smith, Kenneth G.C., and Vinuesa, Carola G.
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Gene expression -- Research ,T cells -- Physiological aspects -- Research ,Estrone -- Physiological aspects -- Research ,Biological sciences ,Health - Abstract
Follicular helper ([T.sub.FH]) cells provide crucial signals to germinal center B cells undergoing somatic hypermutation and selection that results in affinity maturation. Tight control of [T.sub.FH] numbers maintains self tolerance. We describe a population of [Foxp3.sup.+] [Blimp-1.sup.+] [CD4.sup.+] T cells constituting 10-25% of the CXCR5 high [PD-1.sup.high] [CD4.sup.+] T cells found in the germinal center after immunization with protein antigens. These follicular regulatory T ([T.sub.FR]) cells share phenotypic characteristics with [T.sub.FH] and conventional [Foxp3.sup.+] regulatory T ([T.sub.reg]) cells yet are distinct from both. Similar to [T.sub.FH] cells, [T.sub.FR] cell development depends on Bcl-6, SLAM-associated protein (SAP), CD28 and B cells; however, [T.sub.FR] cells originate from thymic-derived [Foxp3.sup.+] precursors, not naive or [T.sub.FH] cells. [T.sub.FR] cells are suppressive in vitro and limit [T.sub.FH] cell and germinal center B cell numbers in vivo. In the absence of [T.sub.FR] cells, an outgrowth of non--antigen-specific B cells in germinal centers leads to fewer antigen- specific cells. Thus, the [T.sub.FH] differentiation pathway is co-opted by [T.sub.reg] cells to control the germinal center response., Germinal centers are clusters of rapidly dividing B cells formed in secondary lymphoid tissues in response to T-dependent antigens. Within the germinal center, mutation of the B receptor cell V-region [...]
- Published
- 2011
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