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B Cell Receptor Crosstalk: BCR Signaling Via the Alternate and Classical Pathways Induces Expression and Secretion of the Autoimmunity‐Associated Cytokine, Osteopontin
Author(s) -
Guo Benchang,
Rothstein Thomas L
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.668.14
Subject(s) - breakpoint cluster region , crosstalk , signal transduction , cytokine , osteopontin , microbiology and biotechnology , autoimmunity , b cell receptor , secretion , biology , interleukin 10 , receptor , cancer research , immunology , chemistry , b cell , endocrinology , immune system , antibody , biochemistry , physics , optics
Classical BCR signaling requires a number of signalosome mediators that are bypassed when BCR signaling follows an alternate pathway produced by prior exposure of B cells to IL‐4. The two pathways, classical and alternate, co‐exist in IL‐4‐treated B cells. Objective: To explore the biological significance of the IL‐4 induced alternate signaling pathway. Methods: Micro array, Real‐time PCR, Western blot, and ELISA were employed. Results: Operation of the IL‐4‐induced alternate pathway changes the nature of the B cell response to BCR engagement so that the cytokine, osteopontin (Opn), is produced. Although Opn expression by B cells has not previously been noted, anti‐Ig‐induced secretion by IL‐4‐treated B cells amounts to levels comparable to those secreted by activated T cells. Unlike T cells, B cell production of Opn does not depend on T‐bet. Conclusions: Because elevated levels of IL‐4 occur in association with severe illnesses, and because Opn is strongly associated with autoimmunity, these results suggest that the IL‐4‐induced alternate BCR signaling pathway may participate in the pathophysiology of autoimmune dyscrasias. This work was supported by Public Health Service grants AI40181 and AI60896 awarded by the National Institutes of Health