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The Role of Vav Proteins in B Cell Responses

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 512))

Abstract

B and T lymphocyte activation mediated through the antigen receptor orchestrates integration of the cell cycle, transcription and differentiation. Furthermore antigen receptor elicited changes in the actin cytoskeleton contribute to the formation of lipid rafts, the movement and directional release of secretory granule contents and the movement of lymphocytes themselves1,2Small GTPases of the Ras HOmolog (Rho) family are widely recognised as regulators of the cytoskeleton, transcription and cell cycle. Rho proteins, including RhoA, Rac-1, Rac-2 and Cdc42 have been shown to regulate the survival, proliferation and differentiation of lymphocytes3. Biochemically, Rho GTPases function as molecular switches, shuttling between an “inactive” GDP-bound state and an “active” GTP-bound state and GTP-bound Rho proteins bind to and control the activity of a great number of effector proteins4,5

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References

  1. Acuto, O. & Cantrell, D. A. T cell activation and the cytoskeleton.Ann. Rev. Immunol. 18,165–184 (2000).

    Article  CAS  Google Scholar 

  2. Dustin, M. L. & Cooper, J. A. The immunological synapse and the actin cytoskeleton: molecular hardware for T cell signaling.Nat. Immunol. 1,23–29 (2000).

    Article  CAS  PubMed  Google Scholar 

  3. Henning, S. W. & Cantrell, D. A. GTPases in antigen receptor signalling.Curr. Opin. Immunol. 10,322–329 (1998).

    Article  CAS  PubMed  Google Scholar 

  4. Van Aelst, L. & D’Souza-Schorey, C. Rho GTPases and signalling networks.Gen. Dev. 11,2295–2322 (1997).

    Article  CAS  Google Scholar 

  5. Bishop, A. B. & Hall, A. Rho GTPases and their effector proteins.Biochem. J. 348,241–255 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bustelo, X. R. Regulatory and Signalling Properties of the Vav Family.Mol. Cell. Biol. 20,1461–1477 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Turner, M.et al.A requirement for the Rho-Family GTP Exchange Factor Vav in Positive and Negative Selection of Thymocytes.Immunity 7, 451–460 (1997).

    Article  CAS  PubMed  Google Scholar 

  8. Kong, Y. Y.et al.Vav regulates peptide-specific apoptosis in thymocytes.J. Exp. Med. 188,2099–2111 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Fischer, K. D.et al.Vav is a regulator of cytoskeletal reorganisation mediated by the T-cell receptor.Curr. Biol.8, 554–562 (1998).

    Article  CAS  PubMed  Google Scholar 

  10. Holsinger, L. J.et al.Defects in actin-cap formation in Vav-deficient mice implicate an actin requirement for lymphocyte signal transduction.Curr. Biol.8, 563–572 (1998).

    Article  CAS  PubMed  Google Scholar 

  11. Costello, P. S.et al.The Rho-family GTP exchange factor Vav is a critical transducer of T cell receptor signals to the calcium, ERK, and NF-kappaB pathways.Proc. Natl. Acad. Sci. U.S.A. 96,3035–3040 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tarakhovsky, A.et al.Defective antigen receptor-mediated proliferation of B and T cells in the absence of Vay.Nature 374,467–470 (1995).

    Article  CAS  PubMed  Google Scholar 

  13. Zhang, R., Alt, F. W., Davidson, L., Orkin, S. H. & Swat, W. Defective signalling through the T- and B-cell antigen receptors in lymphoid cells lacking the vav proto-oncogene.Nature 374,470–473 (1995).

    Article  CAS  PubMed  Google Scholar 

  14. Gulbranson-Judge, A.et al.Defective immunoglobulin class switching in Vav-deficient mice is attributable to compromised T cell help.Eur. J. Immunol. 29,477–487 (1999).

    Article  CAS  PubMed  Google Scholar 

  15. Bachmann, M. F.et al.The guanine-nucleotide exchange factor Vav is a crucial regulator of B cell receptor activation and B cell responses to nonrepetitive antigens.J. Immunol. 163,137–142 (1999).

    CAS  PubMed  Google Scholar 

  16. Billadeau, D. D., Mackie, S. M., Schoon, R. A. & Leibson, P. J. The Rho family Guanine Nucleotide Excahnge factor Vav-2 regulates the Development of Cell-mediated Cytotoxicity.J. Exp. Med. 192,381–391 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Moores, S. L.et al.Vav Family Proteins couple to Diverse Cell Surface Receptors.Mol. Cell. Biol. 20,6364–6373 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Doody, G. M.et al.Vav-2 controls NFAT-dependent transcription in B-but not T-lymphocytes.EMBO. J. 19,6173–6184 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Doody, G. M.et al.Signal transduction through Vav-2 participates in humoral immune responses and B cell maturation.Nat.Immunol., 542–547 (2001).

    Google Scholar 

  20. Soisson, S. M., Nimnual, A. S., Uy, M., Bar-Sagi-D. & Kuriyan, J. Crystal structure of the Dbl and Pleckstrin Homology Domains from the Human Son of Sevenless Protein.Cell 95,259–268 (1998).

    CAS  Google Scholar 

  21. Guinamard, R., Okigaki, M., Schlessinger, J. & Ravetch, J. V. Absence of marginal zone B cells in Pyk-2deficient mice defines their role in the humoral response.Nat. Immunol. 1,31–36 (2000).

    CAS  PubMed  Google Scholar 

  22. Sato, S., Steeber, D. A., Jansen, P. J. & Tedder, T. F. CD19 expression levels regulate B lymphocyte development: human CD1 9 restores normal function in mice lacking endogenous CD19.J. Immunol. 158,4662–4669 (1997).

    CAS  PubMed  Google Scholar 

  23. Gardby, E. & Lycke, N. Y. CD19-deficient mice exhibit poor responsiveness to oral immunisation despite evidence of unaltered total IgA levels, germinal centre and IgA-isotype switching in peyer’s patches.Eur. J. Immunol. 30,1861–1871 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Krawczyk, C.et al.Cbl-b is a negative regulator of receptor clustering and raft aggregation in T cells.Immunity 13,463–473 (2000).

    Article  CAS  PubMed  Google Scholar 

  25. Hardy, R. R., Carmack, C. E., Shinton, S. A., Kemp, J. D. & Hayakama, K. Resolution and characterisation of Pro-B and Pre-Pre-B cell stages in normal mouse bone marrow.J. Exp. Med. 173,1213–1225 (1991).

    Article  CAS  PubMed  Google Scholar 

  26. Allman, D. M., Ferguson, S. E. & Cancro, M. P. Peripheral B cell maturation. I. Immature peripheral B cells in adults are heat-stable antigenhl and exhibit unique signaling characteristics.J. Immunol. 149,2533–2540 (1992).

    CAS  PubMed  Google Scholar 

  27. Allman, D. M., Ferguson, S. E., Lentz, V. M. & Cancro, M. P. Peripheral B cell maturation. II. Heat-stableantigen(hi)splenic B cells are an immature developmental intermediate in the production of long-lived marrow-derived B cells.J. Immunol. 151,4431–4444 (1993).

    CAS  PubMed  Google Scholar 

  28. Loder, F.et al.B cell development in the spleen takes place in discrete steps and is determined by the quality of B cell receptor-derived signals.J. Exp. Med. 190,75–89 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Meffre, E., Casellas, R. & Nussenzweig, M. C. Antibody regulation of B cell development.Nat. Immunol.1, 379–385 (2000).

    Article  CAS  PubMed  Google Scholar 

  30. Lam, K. P., Kuhn, R. & Rajewsky, K.In vivoablation of surface Ig on mature B cells by inducible gene targeting results in rapid cell death.Cell90, 1073–1083 (1997).

    Article  CAS  PubMed  Google Scholar 

  31. Bijsterbosch, M. K., Meade, C. J., Turner, G. A. & Klaus, G. G. B. Blymphocyte receptors and polyphosphoinositide degradation.Cell41, 999–1006 (1985).

    Article  Google Scholar 

  32. Healy, J. I. & Goodnow, C. C. Positive versus negative signaling by lymphocyte antigen receptors.Ann. Rev. Immunol.16, 645–670 (1998).

    Article  CAS  Google Scholar 

  33. Satterthwaite, A. B., Li, Z. & Witte, O. N. Btk function in B cell development and response.Semin. Immunal. 10,309–316 (1998).

    Article  CAS  Google Scholar 

  34. Fruman, D. A., Satterthwaite, A. B.&Witte, O. N. Xid-like Phenotypes: A B cell signalosome takes shape.Immunity13, 1–3 (2000).

    CAS  Google Scholar 

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Turner, M. (2002). The Role of Vav Proteins in B Cell Responses. In: Gupta, S., Butcher, E., Paul, W. (eds) Lymphocyte Activation and Immune Regulation IX. Advances in Experimental Medicine and Biology, vol 512. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0757-4_4

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  • DOI: https://doi.org/10.1007/978-1-4615-0757-4_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5226-6

  • Online ISBN: 978-1-4615-0757-4

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