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THE ROLE OF PI3K SIGNALLING IN THE B CELL RESPONSE TO ANTIGEN

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Crossroads between Innate and Adaptive Immunity II

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 633))

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References

  1. Anderson, K.E., Coadwell, J., Stephens, L.R. Hawkins, P.T. (1998) Translocation of PDK-1 to the plasma membrane is important in allowing PDK-1 to activate protein kinase B. Curr Biol, 8, 684–691

    Article  Google Scholar 

  2. Anzelon, A.N., Wu, H. Rickert, R.C. (2003) Pten inactivation alters peripheral B lymphocyte fate and reconstitutes CD19 function. Nat Immunol, 4, 287–294

    Article  Google Scholar 

  3. Bi, L., Okabe, I., Bernard, D.J. Nussbaum, R.L. (2002) Early embryonic lethality in mice deficient in the p110beta catalytic subunit of PI 3-kinase. Mamm Genome, 13, 169–172

    Google Scholar 

  4. Bi, L., Okabe, I., Bernard, D.J., Wynshaw-Boris, A. Nussbaum, R.L. (1999) Proliferative defect and embryonic lethality in mice homozygous for a deletion in the p110alpha subunit of phosphoinositide 3-kinase. J Biol Chem, 274, 10963–10968

    Article  Google Scholar 

  5. Bilancio, A., Okkenhaug, K., Camps, M., Emery, J.L., Ruckle, T., Rommel, C. Vanhaesebroeck, B. (2006) Key role of the p110delta isoform of PI3K in B-cell antigen and IL-4 receptor signaling: comparative analysis of genetic and pharmacologic interference with p110delta function in B cells. Blood, 107, 642–650

    Article  Google Scholar 

  6. Chantry, D., Vojtek, A., Kashishian, A., Holtzman, D.A., Wood, C., Gray, P.W., Cooper, J.A. Hoekstra, M.F. (1997) p110delta, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed predominantly in leukocytes. J Biol Chem, 272, 19236–19241

    Article  Google Scholar 

  7. Clayton, E., Bardi, G., Bell, S.E., Chantry, D., Downes, C.P., Gray, A., Humphries, L.A., Rawlings, D., Reynolds, H., Vigorito, E. Turner, M. (2002) A crucial role for the p110delta subunit of phosphatidylinositol 3-kinase in B cell development and activation. J Exp Med, 196, 753–763

    Article  Google Scholar 

  8. Cozine, C.L., Wolniak, K.L. Waldschmidt, T.J. (2005) The primary germinal center response in mice. Curr Opin Immunol, 17, 298–302

    Article  Google Scholar 

  9. Del Nagro, C.J., Otero, D.C., Anzelon, A.N., Omori, S.A., Kolla, R.V. Rickert, R.C. (2005) CD19 function in central and peripheral B-cell development. Immunol Res, 31, 119–131

    Article  Google Scholar 

  10. Di Cristofano, A., Pesce, B., Cordon-Cardo, C. Pandolfi, P.P. (1998) Pten is essential for embryonic development and tumour suppression. Nat Genet, 19, 348–355

    Article  Google Scholar 

  11. Eickholt, B.J., Ahmed, A.I., Davies, M., Papakonstanti, E.A., Pearce, W., Starkey, M.L., Bilancio, A., Need, A.C., Smith, A.J., Hall, S.M., Hamers, F.P., Giese, K.P., Bradbury, E.J. Vanhaesebroeck, B. (2007) Control of axonal growth and regeneration of sensory neurons by the p110delta PI 3-kinase. PLoS ONE, 2, e869

    Article  Google Scholar 

  12. Fruman, D.A. (2004) Phosphoinositide 3-kinase and its targets in B-cell and T-cell signaling. Curr Opin Immunol, 16, 314–320

    Article  Google Scholar 

  13. Fruman, D.A., Snapper, S.B., Yballe, C.M., Davidson, L., Yu, J.Y., Alt, F.W. Cantley, L.C. (1999) Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85alpha. Science, 283, 393–397

    Article  Google Scholar 

  14. Hawkins, P.T., Anderson, K.E., Davidson, K. Stephens, L.R. (2006) Signalling through class I PI3Ks in mammalian cells. Biochem Soc Trans, 34, 647–662

    Article  Google Scholar 

  15. Hirsch, E., Katanaev, V.L., Garlanda, C., Azzolino, O., Pirola, L., Silengo, L., Sozzani, S., Mantovani, A., Altruda, F. Wymann, M.P. (2000) Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Science, 287, 1049–1053

    Article  Google Scholar 

  16. Jou, S.T., Carpino, N., Takahashi, Y., Piekorz, R., Chao, J.R., Carpino, N., Wang, D. Ihle, J.N. (2002) Essential, nonredundant role for the phosphoinositide 3-kinase p110delta in signaling by the B-cell receptor complex. Mol Cell Biol, 22, 8580–8591

    Article  Google Scholar 

  17. Maehama, T. Dixon, J.E. (1998) The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem, 273, 13375–13378

    Article  Google Scholar 

  18. Muto, A., Tashiro, S., Nakajima, O., Hoshino, H., Takahashi, S., Sakoda, E., Ikebe, D., Yamamoto, M. Igarashi, K. (2004) The transcriptional programme of antibody class switching involves the repressor Bach2. Nature, 429, 566–571

    Article  Google Scholar 

  19. Ochiai, K., Katoh, Y., Ikura, T., Hoshikawa, Y., Noda, T., Karasuyama, H., Tashiro, S., Muto, A. Igarashi, K. (2006) Plasmacytic transcription factor Blimp-1 is repressed by Bach2 in B cells. J Biol Chem, 281, 38226–38234

    Article  Google Scholar 

  20. Okada, T., Maeda, A., Iwamatsu, A., Gotoh, K. Kurosaki, T. (2000) BCAP: the tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activation. Immunity, 13, 817–827

    Article  Google Scholar 

  21. Okkenhaug, K., Bilancio, A., Farjot, G., Priddle, H., Sancho, S., Peskett, E., Pearce, W., Meek, S.E., Salpekar, A., Waterfield, M.D., Smith, A.J. Vanhaesebroeck, B. (2002) Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice. Science, 297, 1031–1034

    Google Scholar 

  22. Okkenhaug, K. Vanhaesebroeck, B. (2003) PI3K in lymphocyte development, differentiation and activation. Nat Rev Immunol, 3, 317–330

    Article  Google Scholar 

  23. Oliver, A.M., Martin, F., Gartland, G.L., Carter, R.H. Kearney, J.F. (1997) Marginal zone B cells exhibit unique activation, proliferative and immunoglobulin secretory responses. Eur J Immunol, 27, 2366–2374

    Article  Google Scholar 

  24. Omori, S.A., Cato, M.H., Anzelon-Mills, A., Puri, K.D., Shapiro-Shelef, M., Calame, K. Rickert, R.C. (2006) Regulation of class-switch recombination and plasma cell differentiation by phosphatidylinositol 3-kinase signaling. Immunity, 25, 545–557

    Article  Google Scholar 

  25. Omori, S.A. Rickert, R.C. (2007) Phosphatidylinositol 3-kinase (PI3K) signaling and regulation of the antibody response. Cell Cycle, 6, 397–402

    Google Scholar 

  26. Petersen, S., Casellas, R., Reina-San-Martin, B., Chen, H.T., Difilippantonio, M.J., Wilson, P.C., Hanitsch, L., Celeste, A., Muramatsu, M., Pilch, D.R., Redon, C., Ried, T., Bonner, W.M., Honjo, T., Nussenzweig, M.C. Nussenzweig, A. (2001) AID is required to initiate Nbs1/gamma-H2AX focus formation and mutations at sites of class switching. Nature, 414, 660–665

    Article  Google Scholar 

  27. Phan, T.G., Paus, D., Chan, T.D., Turner, M.L., Nutt, S.L., Basten, A. Brink, R. (2006) High affinity germinal center B cells are actively selected into the plasma cell compartment. J Exp Med, 203, 2419–2424

    Article  Google Scholar 

  28. Scheid, M. (2002) PIP3 is essential but not sufficient for protein kinase B activation; PIP2 is required for PKB phosphorylation at ser-473. J Biol Chem, 277, 9027–9035

    Article  Google Scholar 

  29. Shapiro-Shelef, M. Calame, K. (2005) Regulation of plasma-cell development. Nat Rev Immunol, 5, 230–242

    Article  Google Scholar 

  30. Shen, W.H., Balajee, A.S., Wang, J., Wu, H., Eng, C., Pandolfi, P.P. Yin, Y. (2007) Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell, 128, 157–170

    Article  Google Scholar 

  31. Suzuki, A., Pompa, J.L., de la Stambolic, V., Elia, A.J., Sasaki, T., Barco Barrantes, I., del Ho, A., Wakeham, A., Itie, A., Khoo, W., Fukumoto, M. Mak, T.W. (1998) High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol, 8, 1169–1178

    Article  Google Scholar 

  32. Suzuki, A., Kaisho, T., Ohishi, M., Tsukio-Yamaguchi, M., Tsubata, T., Koni, P.A., Sasaki, T., Mak, T.W. Nakano, T. (2003) Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination. J Exp Med, 197, 657–667

    Article  Google Scholar 

  33. Suzuki, H., Terauchi, Y., Fujiwara, M., Aizawa, S., Yazaki, Y., Kadowaki, T. Koyasu, S. (1999) Xid-like immunodeficiency in mice with disruption of the p85alpha subunit of phosphoinositide 3-kinase. Science, 283, 390–392

    Article  Google Scholar 

  34. Vanhaesebroeck, B., Welham, M.J., Kotani, K., Stein, R., Warne, P.H., Zvelebil, M.J., Higashi, K., Volinia, S., Downward, J. Waterfield, M.D. (1997) P110delta, a novel phosphoinositide 3-kinase in leukocytes. Proc Natl Acad Sci USA, 94, 4330–4335

    Article  Google Scholar 

  35. Vigorito, E., Bardi, G., Glassford, J., Lam, E.W., Clayton, E. Turner, M. (2004) Vav-dependent and vav-independent phosphatidylinositol 3-kinase activation in murine B cells determined by the nature of the stimulus. J Immunol, 173, 3209–3214

    Google Scholar 

  36. Vigorito, E. Turner, M. (2006) Differential requirements of PI3K subunits for BCR or BCR/CD19-induced ERK activation. Adv Exp Med Biol, 584, 43–52

    Article  Google Scholar 

  37. Yamazaki, T., Takeda, K., Gotoh, K., Takeshima, H., Akira, S. Kurosaki, T. (2002) Essential immunoregulatory role for BCAP in B cell development and function. J Exp Med, 195, 535–545

    Article  Google Scholar 

  38. Yoshida, C., Yoshida, F., Sears, D.E., Hart, S.M., Ikebe, D., Muto, A., Basu, S., Igarashi, K. Melo, J.V. (2007) Bcr-Abl signaling through the PI-3/S6 kinase pathway inhibits nuclear translocation of the transcription factor Bach2, which represses the antiapoptotic factor heme oxygenase-1. Blood, 109, 1211–1219

    Article  Google Scholar 

  39. Janas M, Hodson D et al. The effect of deleting p110delta on the phenotype and function of PTEN-deficient B cells. J. Immunol. 2008 Jan 15;180(2):739–46.

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank our colleagues for many stimulating discussions. DJH is a Cancer Research UK McElwain Clinical Research Training Fellow and MT is a Senior Non-Clinical Fellow of the Medical Research Council. Both are additionally supported by the Biotechnology and Biological Sciences Research Council.

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Authors and Affiliations

  1. Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 2AT, UK

    Daniel J. Hodson

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  1. Daniel J. Hodson
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  2. Martin Turner
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Editors and Affiliations

  1. Immunology, La Jolla Institute for Allergy &, Science Center Drive 10355 , San Diego, 92121, U.S.A.

    Stephen P. Schoenberger

  2. College of Medicine, Drexel University, Queen Lane 2900, Philadelphia, 19129, U.S.A.

    Peter D. Katsikis

  3. Emory Vaccine Center &, Emory University, Gatewood Rd. 954, Atlanta, 30329, U.S.A.

    Bali Pulendran

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Hodson, D., Turner, M. (2009). THE ROLE OF PI3K SIGNALLING IN THE B CELL RESPONSE TO ANTIGEN. In: Schoenberger, S., Katsikis, P., Pulendran, B. (eds) Crossroads between Innate and Adaptive Immunity II. Advances in Experimental Medicine and Biology, vol 633. Springer, New York, NY. https://doi.org/10.1007/978-0-387-79311-5_5

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