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Original Article

Chang H. Kim^a,b, Lusijah S. Rott^a,b, Ian Clark-Lewis^c, Daniel J. Campbell^a,b, Lijun Wu^d, and Eugene C. Butcher^a,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
Stanford University, PAVAH 154B, Bldg. 101, Rm. C4-111, 3801 Miranda Ave., Palo Alto, CA 94304-1207.650-858-3986650-493-5000 ext. 63167

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

© 2001 The Rockefeller University Press

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