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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.
Submitted August 6, 2003
Accepted November 18, 2003
BAFF/BLyS can potentiate B-cell selection with the B-cell co-receptor complex
Hidenori Hase, Yumiko Kanno, Masaru Kojima, Kaoru Hasegawa, Daisuke Sakurai, Hidefumi Kojima, Naoyuki Tsuchiya, Katsushi Tokunaga, Nobuhide Masawa, Miyuki Azuma, Ko Okumura, and Tetsuji Kobata*
Division of Immunology, Institute for Medical Science, Dokkyo University School of Medicine, Tochigi, Japan
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, Tokyo, Japan
Department of Molecular Immunology, Tokyo Medical and Dental University, Tokyo, Japan
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
* Corresponding author; email: tkobata{at}dokkyomed.ac.jp.
The TNF-like ligand BAFF/BLyS 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-cell specific transcription factor Pax5/BSAP activity and its target CD19, a major component of the B-cell co-receptor complex, and synergistically enhanced CD19 phosphorylation by B-cell antigen receptor (BCR). BAFF further enhanced B-cell proliferation, IgG production and reactivity to CD154 by BCR/CD19 co-ligation and IL-15. Our results suggest that BAFF may play an important role in FDC-B-cell interactions through the B-cell co-receptor complex and a possibly sequential link between the T-cell-independent and -dependent B-cell responses in the germinal centers.
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