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. 1987 Dec;84(23):8588–8592. doi: 10.1073/pnas.84.23.8588

B-lymphocyte activation mediated by anti-immunoglobulin antibody in the absence of protein kinase C.

J J Mond 1, N Feuerstein 1, F D Finkelman 1, F Huang 1, K P Huang 1, G Dennis 1
PMCID: PMC299590  PMID: 3500475

Abstract

B-cell activation induced by crosslinking of surface immunoglobulin is known to stimulate hydrolysis of phosphatidylinositol to diacylglycerol and inositol trisphosphate. We now provide evidence that alternative pathways of activation may also be recruited during such activation. We utilized depletion of protein kinase C activity to determine whether this enzyme is required under all conditions for anti-immunoglobulin-stimulated B-cell activation. Although anti-immunoglobulin does not induce B-cell proliferation in protein kinase C-depleted cells, it stimulates an earlier event in B-cell activation as reflected by its ability to enhance the expression of major histocompatibility complex-encoded class II molecules. Furthermore, the ribonucleoside 8-mercaptoguanosine restores the ability of anti-immunoglobulin to induce B-cell proliferation in protein kinase C-depleted cells. This restoration is also demonstrated by an enhancement of synthesis of a nuclear protein that we find is increased during B-cell mitogenesis. These results indicate that B-cell activation stimulated by anti-immunoglobulin may recruit pathways in addition to the one dependent on protein kinase C.

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Selected References

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  1. Besterman J. M., Duronio V., Cuatrecasas P. Rapid formation of diacylglycerol from phosphatidylcholine: a pathway for generation of a second messenger. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6785–6789. doi: 10.1073/pnas.83.18.6785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bijsterbosch M. K., Meade C. J., Turner G. A., Klaus G. G. B lymphocyte receptors and polyphosphoinositide degradation. Cell. 1985 Jul;41(3):999–1006. doi: 10.1016/s0092-8674(85)80080-5. [DOI] [PubMed] [Google Scholar]
  3. Bodnar J. W., Jones C. J., Coombs D. H., Pearson G. D., Ward D. C. Proteins tightly bound to HeLa cell DNA at nuclear matrix attachment sites. Mol Cell Biol. 1983 Sep;3(9):1567–1579. doi: 10.1128/mcb.3.9.1567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Braun J., Sha'afi R. I., Unanue E. R. Crosslinking by ligands to surface immunoglobulin triggers mobilization of intracellular 45Ca2+ in B lymphocytes. J Cell Biol. 1979 Sep;82(3):755–766. doi: 10.1083/jcb.82.3.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cambier J. C., Monroe J. G. B cell activation. V. Differentiation signaling of B cell membrane depolarization, increased I-A expression, G0 to G1 transition, and thymidine uptake by anti-IgM and anti-IgD antibodies. J Immunol. 1984 Aug;133(2):576–581. [PubMed] [Google Scholar]
  6. Chambard J. C., Paris S., L'Allemain G., Pouysségur J. Two growth factor signalling pathways in fibroblasts distinguished by pertussis toxin. Nature. 1987 Apr 23;326(6115):800–803. doi: 10.1038/326800a0. [DOI] [PubMed] [Google Scholar]
  7. Chen Z. Z., Coggeshall K. M., Cambier J. C. Translocation of protein kinase C during membrane immunoglobulin-mediated transmembrane signaling in B lymphocytes. J Immunol. 1986 Mar 15;136(6):2300–2304. [PubMed] [Google Scholar]
  8. Coggeshall K. M., Cambier J. C. B cell activation. VIII. Membrane immunoglobulins transduce signals via activation of phosphatidylinositol hydrolysis. J Immunol. 1984 Dec;133(6):3382–3386. [PubMed] [Google Scholar]
  9. Coughlin S. R., Lee W. M., Williams P. W., Giels G. M., Williams L. T. c-myc gene expression is stimulated by agents that activate protein kinase C and does not account for the mitogenic effect of PDGF. Cell. 1985 Nov;43(1):243–251. doi: 10.1016/0092-8674(85)90029-7. [DOI] [PubMed] [Google Scholar]
  10. Feuerstein N., Ali I. U. Comparative analysis of p21 proteins from various cell types by two-dimensional gel electrophoresis. J Cell Biochem. 1985;29(3):253–263. doi: 10.1002/jcb.240290309. [DOI] [PubMed] [Google Scholar]
  11. Finkelman F. D., Kessler S. W., Mushinski J. F., Potter M. IgD-secreting murine plasmacytomas: identification and partial characterization of two IgD myeloma proteins. J Immunol. 1981 Feb;126(2):680–687. [PubMed] [Google Scholar]
  12. Goodman M. G. Regulation of B cell activation by prostaglandins: cell cycle-specific effects on activation by anti-immunoglobulin and 8-mercaptoguanosine. J Immunol. 1986 Dec 15;137(12):3753–3757. [PubMed] [Google Scholar]
  13. Grupp S. A., Harmony J. A. Increased phosphatidylinositol metabolism is an important but not an obligatory early event in B lymphocyte activation. J Immunol. 1985 Jun;134(6):4087–4094. [PubMed] [Google Scholar]
  14. Kaibuchi K., Tsuda T., Kikuchi A., Tanimoto T., Yamashita T., Takai Y. Possible involvement of protein kinase C and calcium ion in growth factor-induced expression of c-myc oncogene in Swiss 3T3 fibroblasts. J Biol Chem. 1986 Jan 25;261(3):1187–1192. [PubMed] [Google Scholar]
  15. Klaus G. G., O'Garra A., Bijsterbosch M. K., Holman M. Activation and proliferation signals in mouse B cells. VIII. Induction of DNA synthesis in B cells by a combination of calcium ionophores and phorbol myristate acetate. Eur J Immunol. 1986 Jan;16(1):92–97. doi: 10.1002/eji.1830160118. [DOI] [PubMed] [Google Scholar]
  16. Kraft A. S., Anderson W. B. Phorbol esters increase the amount of Ca2+, phospholipid-dependent protein kinase associated with plasma membrane. Nature. 1983 Feb 17;301(5901):621–623. doi: 10.1038/301621a0. [DOI] [PubMed] [Google Scholar]
  17. Krebs E. G., Beavo J. A. Phosphorylation-dephosphorylation of enzymes. Annu Rev Biochem. 1979;48:923–959. doi: 10.1146/annurev.bi.48.070179.004423. [DOI] [PubMed] [Google Scholar]
  18. Leibson H. J., Marrack P., Kappler J. W. B cell helper factors. I. Requirement for both interleukin 2 and another 40,000 mol wt factor. J Exp Med. 1981 Nov 1;154(5):1681–1693. doi: 10.1084/jem.154.5.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lindsten T., Thompson C. B., Finkelman F. D., Andersson B., Scher I. Changes in the expression of B cell surface markers on complement receptor-positive and complement receptor-negative B cells induced by phorbol myristate acetate. J Immunol. 1984 Jan;132(1):235–239. [PubMed] [Google Scholar]
  20. Mishell R. I., Dutton R. W. Immunization of dissociated spleen cell cultures from normal mice. J Exp Med. 1967 Sep 1;126(3):423–442. doi: 10.1084/jem.126.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mizuguchi J., Beaven M. A., Ohara J., Paul W. E. BSF-1 action on resting B cells does not require elevation of inositol phospholipid metabolism or increased [Ca2+]i. J Immunol. 1986 Oct 1;137(7):2215–2219. [PubMed] [Google Scholar]
  22. Mond J. J., Seghal E., Kung J., Finkelman F. D. Increased expression of I-region-associated antigen (Ia) on B cells after cross-linking of surface immunoglobulin. J Immunol. 1981 Sep;127(3):881–888. [PubMed] [Google Scholar]
  23. Nel A. E., Wooten M. W., Landreth G. E., Goldschmidt-Clermont P. J., Stevenson H. C., Miller P. J., Galbraith R. M. Translocation of phospholipid/Ca2+-dependent protein kinase in B-lymphocytes activated by phorbol ester or cross-linking of membrane immunoglobulin. Biochem J. 1986 Jan 1;233(1):145–149. doi: 10.1042/bj2330145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  25. Noelle R., Krammer P. H., Ohara J., Uhr J. W., Vitetta E. S. Increased expression of Ia antigens on resting B cells: an additional role for B-cell growth factor. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6149–6153. doi: 10.1073/pnas.81.19.6149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
  27. Rodriguez-Pena A., Rozengurt E. Disappearance of Ca2+-sensitive, phospholipid-dependent protein kinase activity in phorbol ester-treated 3T3 cells. Biochem Biophys Res Commun. 1984 May 16;120(3):1053–1059. doi: 10.1016/s0006-291x(84)80213-2. [DOI] [PubMed] [Google Scholar]
  28. Roehm N. W., Leibson H. J., Zlotnik A., Kappler J., Marrack P., Cambier J. C. Interleukin-induced increase in Ia expression by normal mouse B cells. J Exp Med. 1984 Sep 1;160(3):679–694. doi: 10.1084/jem.160.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rothstein T. L., Baeker T. R., Miller R. A., Kolber D. L. Stimulation of murine B cells by the combination of calcium ionophore plus phorbol ester. Cell Immunol. 1986 Oct 15;102(2):364–373. doi: 10.1016/0008-8749(86)90430-2. [DOI] [PubMed] [Google Scholar]
  30. Rothstein T. L., Kolber D. L., Simons E. R., Baeker T. R. Inhibition by phorbol esters of antiimmunoglobulin-induced calcium signalling and B-cell activation. J Cell Physiol. 1986 Dec;129(3):347–355. doi: 10.1002/jcp.1041290313. [DOI] [PubMed] [Google Scholar]
  31. Stabel S., Rodriguez-Pena A., Young S., Rozengurt E., Parker P. J. Quantitation of protein kinase C by immunoblot--expression in different cell lines and response to phorbol esters. J Cell Physiol. 1987 Jan;130(1):111–117. doi: 10.1002/jcp.1041300116. [DOI] [PubMed] [Google Scholar]
  32. Stumpo D. J., Blackshear P. J. Insulin and growth factor effects on c-fos expression in normal and protein kinase C-deficient 3T3-L1 fibroblasts and adipocytes. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9453–9457. doi: 10.1073/pnas.83.24.9453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yamashita T., Tsuda T., Hamamori Y., Takai Y. Possible involvement of cyclic AMP and calcium ion in prostaglandin E1-induced elevation of c-myc mRNA levels in Swiss 3T3 fibroblasts. J Biol Chem. 1986 Dec 25;261(36):16878–16882. [PubMed] [Google Scholar]

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