The Journal of Experimental Medicine
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Published online 18 June 2001.
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© The Rockefeller University Press, 0022-1007/2001/6/1373/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 12, June 18, 2001 1373-1382

Original Article

Subspecialization of CXCR5+ T Cells: B Helper Activity Is Focused in a Germinal Center–localized Subset of CXCR5+ T Cells

Chang H. Kima,b, Lusijah S. Rotta,b, Ian Clark-Lewisc, Daniel J. Campbella,b, Lijun Wud, and Eugene C. Butchera,b
a Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California 94305
b Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304
c Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada BC V6T 1Z3
d Millennium Pharmaceuticals, Incorporated, Cambridge, Massachusetts 02139

Correspondence to: Chang H. Kim, Stanford University, PAVAH 154B, Bldg. 101, Rm. C4-111, 3801 Miranda Ave., Palo Alto, CA 94304-1207. Tel:650-493-5000 ext. 63167 Fax:650-858-3986 E-mail:chkim{at}stanford.edu.

The T helper (Th) cell pool is composed of specialized cells with heterogeneous effector functions. Apart from Th1 and 2 cells, CXCR5+ T cells have been suggested to be another type of effector T cell specialized for B cell help. We show here that CXCR5+ T cells are heterogeneous, and we identify subsets of CXCR5+ CD4 T cells that differ in function and microenvironmental localization in secondary lymphoid tissues. CD57+CXCR5 T cells, hereafter termed germinal center Th (GC-Th) cells, are localized only in GCs, lack CCR7, and are highly responsive to the follicular chemokine B lymphocyte chemoattractant but not to the T cell zone EBI1-ligand chemokine. Importantly, GC-Th cells are much more efficient than CD57-CXCR5+ T cells or CXCR5- T cells in inducing antibody production from B cells. Consistent with their function, GC-Th cells produce elevated levels of interleukin 10 upon stimulation which, with other cytokines and costimulatory molecules, may help confer their B cell helper activity. Our results demonstrate that CXCR5+ T cells are functionally heterogeneous and that the GC-Th cells, a small subset of CXCR5+ T cells, are the key helpers for B cell differentiation and antibody production in lymphoid tissues.

Key Words: germinal center, chemokine receptor, CXCR5, B cell help, T helper cells


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