The Journal of Experimental Medicine
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Published online 4 December 2000.
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© The Rockefeller University Press, 0022-1007/2000/12/1545/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 11, December 4, 2000 1545-1552

Original Article

Follicular B Helper T Cells Express Cxc Chemokine Receptor 5, Localize to B Cell Follicles, and Support Immunoglobulin Production

Dagmar Breitfelda, Lars Ohla, Elisabeth Kremmerb, Joachim Ellwartb, Federica Sallustoc, Martin Lippa, and Reinhold Förstera

a Molecular Tumor and Immunogenetics, Max-Delbrück Center for Molecular Medicine, 13092 Berlin, Germany
b Institute of Molecular Immunology, GSF National Research Center for Environment and Health, 81377 München, Germany
c Institute of Research in Biomedicine, 6500 Belinzona, Switzerland
Max-Delbrück Center for Molecular Medicine, Robert-Rössle Str. 10, D-13092 Berlin, Germany.49-30-9406-388449-30-9406-3330

rfoerst{at}mdc-berlin.de

Chemokines and their receptors have been identified as major regulators controlling the functional organization of secondary lymphoid organs. Here we show that expression of CXC chemokine receptor 5 (CXCR5), a chemokine receptor required for B cell homing to B cell follicles, defines a novel subpopulation of B helper T cells localizing to follicles. In peripheral blood these cells coexpress CD45RO and the T cell homing CC chemokine receptor 7 (CCR7). In secondary lymphoid organs, CD4+CXCR5+ cells lose expression of CCR7, which allows them to localize to B cell follicles and germinal centers where they express high levels of CD40 ligand (CD40L), a costimulatory molecule required for B cell activation and inducible costimulator (ICOS), a recently identified costimulatory molecule of the CD28 family. Thus, when compared with CD4+CD45RO+CXCR5– cells, CD4+CD45RO+CXCR5+ tonsillar T cells efficiently support the production of immunoglobulin (Ig)A and IgG. In contrast, analysis of the memory response revealed that long-lasting memory cells are found within the CD4+CD45RO+CXCR5– population, suggesting that CXCR5+CD4 cells represent recently activated effector cells. Based on the characteristic localization within secondary lymphoid organs, we suggest to term these cells "follicular B helper T cells" (TFH).

Key Words: CXC chemokine receptor 5 • CC chemokine receptor 7 • T cell homing • germinal centers • T helper cells

Abbreviations used in this paper: BLC, B lymphocyte chemoattractant; CCR7, CC chemokine receptor 7; CXCR5, CXC chemokine receptor 5; DC, dendritic cell; ELC, EBV-induced molecule 1 ligand chemokine; FDC, follicular DC; GC, germinal center; HEV, high endothelial venule; ICOS, inducible costimulator; LT, lymphotoxin; SLC, secondary lymphoid tissue chemokine; TCM, central memory T cells; TT, tetanus toxin.

© 2000 The Rockefeller University Press


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