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Blood, 1 October 2004, Vol. 104, No. 7, pp. 1952-1960.
Prepublished online as a Blood First Edition Paper on June 22, 2004; DOI 10.1182/blood-2004-03-1206.
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CHEMOKINES
Unique gene expression program of human germinal center T helper cells
Chang H. Kim,
Hyung W. Lim,
Jong R. Kim,
Lusijah Rott,
Peter Hillsamer, and
Eugene C. Butcher
From the Laboratory of Immunology and Hematopoiesis, Department of Pathobiology, the Purdue Cancer Center, the Bindley Bioscience Center, and the Biochemistry and Molecular Biology Program, Purdue University, West Lafayette, IN; the Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA; the Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA; and Sagamore Surgical Center, Lafayette, IN.
Gene expression profiling was used to compare the gene expression patterns of human germinal center (GC) T helper (Th) cells with other CD4+ T-cell subsets (naive, central, and effector memory T cells). GC-Th cells, specifically localized in germinal centers to help B cells, are distantly related to central and effector memory T cells in global gene expression profiles. GC-Th cells displayed substantial differences in mRNA for adhesion molecules, chemoattractant receptors, and cytokines compared with other populations. Distinct expression of transcriptional factors by GC-Th cells is consistent with the hypothesis that they may be different from other T cells in cell lineage. Interestingly, CXCL13, a critical chemokine for B-cell entry to lymphoid follicles, is one of the most highly up-regulated genes in GC-Th cells. GC-Th cells (but not other T cells) produce and secrete large amounts of functional CXCL13 upon T-cell receptor activation, a process that is dependent on costimulation, requires translation and transcription, and is dramatically enhanced by activation in the presence of GC-B cells. This study revealed for the first time the unique gene expression program of GC-Th cells.
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