The Journal of Experimental Medicine
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Published online 4 December 2000.
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© The Rockefeller University Press, 0022-1007/2000/12/1553/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 11, December 4, 2000 1553-1562

Original Article

Cxc Chemokine Receptor 5 Expression Defines Follicular Homing T Cells with B Cell Helper Function

Patrick Schaerlia, Katharina Willimanna, Alois B. Langb, Martin Lippc, Pius Loetschera, and Bernhard Mosera

a Theodor-Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland
b BERNA, Swiss Serum and Vaccine Institute, 3018 Bern, Switzerland
c Molecular Tumorgenetics and Immunogenetics, Max-Delbrück Center for Molecular Medicine, 13092 Berlin, Germany
Theodor-Kocher Institute, University of Bern, P.O. Box 99, CH-3000 Bern 9, Switzerland.41-31-631-379941-31-631-4160

patrick.schaerli{at}tki.unibe.ch

Leukocyte traffic through secondary lymphoid tissues is finely tuned by chemokines. We have studied the functional properties of a human T cell subset marked by the expression of CXC chemokine receptor 5 (CXCR5). Memory but not naive T cells from tonsils are CXCR5+ and migrate in response to the B cell–attracting chemokine 1 (BCA-1), which is selectively expressed by reticular cells and blood vessels within B cell follicles. Tonsillar CXCR5+ T cells do not respond to other chemokines present in secondary lymphoid tissues, including secondary lymphoid tissue chemokine (SLC), EBV-induced molecule 1 ligand chemokine (ELC), and stromal cell–derived factor 1 (SDF-1). The involvement of tonsillar CXCR5+ T cells in humoral immune responses is suggested by their localization in the mantle and light zone germinal centers of B cell follicles and by the concomitant expression of activation and costimulatory markers, including CD69, HLA-DR, and inducible costimulator (ICOS). Peripheral blood CXCR5+ T cells also belong to the CD4+ memory T cell subset but, in contrast to tonsillar cells, are in a resting state and migrate weakly to chemokines. CXCR5+ T cells are very inefficient in the production of cytokines but potently induce antibody production during coculture with B cells. These properties portray CXCR5+ T cells as a distinct memory T cell subset with B cell helper function, designated here as follicular B helper T cells (TFH).

Key Words: chemokines • CXC chemokine receptor 5 • lymphocytes • B cell follicle • antibodies

Abbreviations used in this paper: BCA-1, B cell–attracting chemokine 1; CCR7, CC chemokine receptor 7; CXCR5, CXC chemokine receptor 5; DIG, digoxigenin; ELC, EBV-induced molecule 1 ligand chemokine; HEV, high endothelial venule; HPF, high power field; ICOS, inducible costimulator; PP, Peyer's patch; SDF-1, stromal cell–derived factor 1; SLC, secondary lymphoid tissue chemokine; TBS, Tris-buffered saline.

© 2000 The Rockefeller University Press


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