Foxp3+ Follicular Regulatory T Cells Control the Germinal Center Response

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2011 Jul 26

PMID 21785433

Citations 716

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

Affiliations

Soon will be listed here.

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.

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