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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 #
Issue Date: 24-Jul-2011
Publisher: Nature Pub. Co.
Series Title: Nature Medicine vol:17 issue:8 pages:975-82
Article number: 10.1038/nm.2425
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.
URI: 
ISSN: 1078-8956
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Genetics of Autoimmunity
× corresponding author
# (joint) last author

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