The B cell receptor (BCR) complex engages antigen through surface immunoglobulin and in so doing triggers a series of biochemical events that transduce the initial extracellular binding event to intracellular milieu, producing changes that ultimately specify B cell behavior. In the process of B cell activation, cytokines such as IL-4 play synergistic role with antigen engagement. In the past several years, we found that IL-4 could induce alternate pathway in primary B cells. In naïve B cell, ERK activation by BCR engagement is mediated by signalosome, while in IL-4 pretreated B cells, ERK are activated by two pathways: one is signalosome mediated classical pathway, the other is signalosome independent alternate pathway, which is mediated by Lyn and RasGRP1. The two pathways paralleled operated in IL-4 pretreated cells.

Ostepontin (Opn) is an autoimmunity-associated cytokine. Activated naïve B cells do not express Opn, while IL-4 pretreated B cells express Opn upon BCR engagement. Furthermore we found that this B cells derived Opn is mediated by not only classical pathway but also alternate pathway. The proposal of this project is to investigate whether B cell derived Opn is involved in the pathogenesis of autoimmune disease.  On the other hand, the understanding of potential role of B cell derived Opn will shine insight in not only the elucidation the mechanism of pathogenesis of autoimmune disease but also the development of therapy for autoimmunity.

B1 cells are main source for natural antibody such as IgM, which is vital for defense of infection. Xid mice, due to defective B1 cell development in peritoneal cavity, are susceptible to infection with streptococcus pneumoniae. We found that B1b was restored when crossed xid mice with IL-4 transgenic mice.  We will ask: 1. Whether the development of B1b cell is mediated by IL-4 induced alternate pathway. 2. Whether the restored B1b is able to produce the protection for the infection of streptococcus pneumoniae.

Publications:

Guo B., Tumang J.R., Rothsein T.L.  B Cell Receptor Crosstalk: B Cells Express Osteopontin Through the Combined Action of the Alternate and Classical BCR signaling Pathways. Mol Immunol. 2009 46(4):587-91

Dye J.R., Guo B, and Rothstein.TL. B cell receptor cross-talk: exposure to lipopolysaccharide induces an alternate pathway for B cell receptor-induced ERK phosphorylation and NF-kappa B activation.. J Immunol. 2007 179(1):229-235.

Guo B, Blair D, Chiles TC, Lowell CA, Rothstein TL. Cutting Edge: B cell receptor (BCR) cross-talk: the IL-4-induced alternate pathway for BCR signaling operates in parallel with the classical pathway, is sensitive to Rottlerin, and depends on Lyn. J Immunol. 2007 178(8): 4726-4730.

Guo B, Rothstein TL. B cell receptor (BCR) cross-talk: IL-4 creates an alternate pathway for BCR-induced ERK activation that is phosphatidylinositol 3-kinase   independent. J Immunol. 2005 174(9): 5375-5381.

Guo B and Xu y. Anti-human hepatocellular carcinoma effects of tumor necrosis factor-related apoptosis-inducing ligand in vitro & in vivo. Acta Pharmacolgica Sinica. 2001 Sep; 22(9): 831-836.

Guo B. and Xu y. Bcl-2 over-expression and activation of protein kinase C suppress the trail-induced apoptosis in Jurkat T cells. Cell Research. 2001 Jun; 11 (2): 101-106.

Chen, Y., Yu C., Guo B., et al. Cloning and functional expression of CPP32 cDNA in E. coli. Prog. Biochem. Biophys. 1998. 25:151-154.

Chen Y., Wen L., Yu C., Guo B., et al. Cloning and expression of Bcl-xLand Bcl-xs cDNA. High Technology Letters. 1996 6(4): 1-3.

Chen Y., Guo B., Wen L. Bak gene and Bcl-2 family. Foreign Science (Molecular Biology). 1996 1896: 260-263.

Guo B and  Shu W. Detection of Trachoma Chlamydia by PCR.Chinese Journal of Zoonoses. 1995 11(6): 48-51.

Huang J., Zeng G., Chen Y., Guo B., Wen L. The expression and activity assay of human TNF deivative cDNA in E.coli. Journal of Xiamen University (natural Science). 1995 35(5): 787-789.