BAFF/BLyS can potentiate B-cell selection with the B-cell coreceptor complex

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 dend...

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Bibliographic Details
Published in:Blood 2004-03, Vol.103 (6), p.2257-2265
Main Authors: Hase, Hidenori, Kanno, Yumiko, Kojima, Masaru, Hasegawa, Kaoru, Sakurai, Daisuke, Kojima, Hidefumi, Tsuchiya, Naoyuki, Tokunaga, Katsushi, Masawa, Nobuhide, Azuma, Miyuki, Okumura, Ko, Kobata, Tetsuji
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal
Antigens, CD19 - metabolism
B-Cell Activating Factor
B-Lymphocytes - metabolism
Biological and medical sciences
CD40 Ligand - metabolism
Dendritic Cells - metabolism
DNA-Binding Proteins - metabolism
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Germinal Center - cytology
Humans
Immunobiology
Interleukin-15 - metabolism
Membrane Proteins - genetics
Membrane Proteins - metabolism
Modulation of the immune response (stimulation, suppression)
PAX5 Transcription Factor
Phosphorylation
Receptors, Tumor Necrosis Factor - metabolism
Transcription Factors - metabolism
Transfection
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - metabolism
Up-Regulation - immunology
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Summary: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 cell–specific transcription factor Pax5/BSAP (Pax5/B cell–specific 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 FDC–B-cell interactions through the B-cell coreceptor complex and a possibly sequential link between the T cell–independent and –dependent B-cell responses in the germinal centers.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2003-08-2694