Foxp3+ follicular regulatory T cells control the germinal center response View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-08

AUTHORS

Michelle A Linterman, Wim Pierson, Sau K Lee, Axel Kallies, Shimpei Kawamoto, Tim F Rayner, Monika Srivastava, Devina P Divekar, Laura Beaton, Jennifer J Hogan, Sidonia Fagarasan, Adrian Liston, Kenneth G C Smith, Carola G Vinuesa

ABSTRACT

Follicular helper (T(FH)) cells provide crucial signals to germinal center B cells undergoing somatic hypermutation and selection that results in affinity maturation. Tight control of T(FH) numbers maintains self tolerance. We describe a population of Foxp3(+)Blimp-1(+)CD4(+) T cells constituting 10-25% of the CXCR5(high)PD-1(high)CD4(+) T cells found in the germinal center after immunization with protein antigens. These follicular regulatory T (T(FR)) cells share phenotypic characteristics with T(FH) and conventional Foxp3(+) regulatory T (T(reg)) cells yet are distinct from both. Similar to T(FH) cells, T(FR) cell development depends on Bcl-6, SLAM-associated protein (SAP), CD28 and B cells; however, T(FR) cells originate from thymic-derived Foxp3(+) precursors, not naive or T(FH) cells. T(FR) cells are suppressive in vitro and limit T(FH) cell and germinal center B cell numbers in vivo. In the absence of T(FR) cells, an outgrowth of non-antigen-specific B cells in germinal centers leads to fewer antigen-specific cells. Thus, the T(FH) differentiation pathway is co-opted by T(reg) cells to control the germinal center response. More... »

PAGES

975

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm.2425

DOI

http://dx.doi.org/10.1038/nm.2425

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1016362145

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21785433


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