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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2257-2265. Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-08-2694.
IMMUNOBIOLOGY BAFF/BLyS can potentiate B-cell selection with the B-cell coreceptor complexFrom the Division of Immunology, Institute for Medical Science, and Department of Pathology, Dokkyo University School of Medicine, Tochigi, Japan; Research Center of Fundamental Medicine, International University of Health and Welfare, Tochigi, Japan; Department of Human Genetics, Graduate School of Medicine, the University of Tokyo, Japan; Department of Molecular Immunology, Tokyo Medical and Dental University, Japan; and Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
The tumor necrosis factor (TNF)like ligand BAFF/BLyS (B-cell activating factor of the TNF family/B-lymphocyte stimulator) is a potent B-cell survival factor, yet its functional relationship with other B-cell surface molecules such as CD19 and CD40 is poorly understood. We found that follicular dendritic cells (FDCs) in human lymph nodes expressed BAFF abundantly. BAFF up-regulated a B cellspecific transcription factor Pax5/BSAP (Pax5/B cellspecific activator protein) activity and its target CD19, a major component of the B-cell coreceptor complex, and synergistically enhanced CD19 phosphorylation by B-cell antigen receptor (BCR). BAFF further enhanced B-cell proliferation, immunoglobulin G (IgG) production, and reactivity to CD154 by BCR/CD19 coligation and interleukin-15 (IL-15). Our results suggest that BAFF may play an important role in FDCB-cell interactions through the B-cell coreceptor complex and a possibly sequential link between the T cellindependent and dependent B-cell responses in the germinal centers.
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