We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Foxp3+ follicular regulatory T cells control the germinal center response.
- Authors
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; Vinuesa, Carola G
- 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.
- Publication
Nature medicine, 2011, Vol 17, Issue 8, p975
- ISSN
1546-170X
- Publication type
Journal Article
- DOI
10.1038/nm.2425