Abstract
In comparison to B cell stimulation mediated by surface immunoglobulin (Ig) antigen receptor ligation, little is known about the intracellular events associated with T cell-dependent B cell responses. A model for the efferent phase of T cell-B cell interaction was used to examine the capacity of activated T cells to trigger nuclear expression of the trans-acting transcription factor, NF-kappa B, in B cells. Fixed, activated, but not fixed, resting Th2 cells were found to induce increased binding activity for a kappa B site-containing oligonucleotide in a time-dependent manner. This induction of NF-kappa B was eliminated by an antibody directed against a 39-kD cell interaction protein on activated T cells as well as by a soluble form of B cell CD40. Of particular relevance to intracellular signaling, NF- kappa B induction was not diminished by prior depletion of B cell protein kinase C (PKC) with phorbol myristate acetate. These results strongly suggest that T cell-dependent B cell stimulation is associated with NF-kappa B induction via p39-CD40 interaction and that this is brought about by non-PKC dependent signaling, in marked contrast to the previously documented requirement for PKC in sIg receptor-mediated stimulation. This suggest that NF-kappa B responds to more than one receptor-mediated intracellular signaling pathway in B cells and may be part of a "final common pathway" for B cell stimulation.
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- Arima N., Kuziel W. A., Grdina T. A., Greene W. C. IL-2-induced signal transduction involves the activation of nuclear NF-kappa B expression. J Immunol. 1992 Jul 1;149(1):83–91. [PubMed] [Google Scholar]
- Baeuerle P. A. The inducible transcription activator NF-kappa B: regulation by distinct protein subunits. Biochim Biophys Acta. 1991 Apr 16;1072(1):63–80. doi: 10.1016/0304-419x(91)90007-8. [DOI] [PubMed] [Google Scholar]
- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
- Cambier J. C., Ransom J. T. Molecular mechanisms of transmembrane signaling in B lymphocytes. Annu Rev Immunol. 1987;5:175–199. doi: 10.1146/annurev.iy.05.040187.001135. [DOI] [PubMed] [Google Scholar]
- Cohen D. P., Rothstein T. L. Elevated levels of protein kinase C activity and alpha-isoenzyme expression in murine peritoneal B cells. J Immunol. 1991 May 1;146(9):2921–2927. [PubMed] [Google Scholar]
- Ghosh S., Baltimore D. Activation in vitro of NF-kappa B by phosphorylation of its inhibitor I kappa B. Nature. 1990 Apr 12;344(6267):678–682. doi: 10.1038/344678a0. [DOI] [PubMed] [Google Scholar]
- Jamieson C., McCaffrey P. G., Rao A., Sen R. Physiologic activation of T cells via the T cell receptor induces NF-kappa B. J Immunol. 1991 Jul 15;147(2):416–420. [PubMed] [Google Scholar]
- Kawakami K., Parker D. C. Antigen and helper T lymphocytes activate B lymphocytes by distinct signaling pathways. Eur J Immunol. 1993 Jan;23(1):77–84. doi: 10.1002/eji.1830230113. [DOI] [PubMed] [Google Scholar]
- Liu J. L., Chiles T. C., Sen R. J., Rothstein T. L. Inducible nuclear expression of NF-kappa B in primary B cells stimulated through the surface Ig receptor. J Immunol. 1991 Mar 1;146(5):1685–1691. [PubMed] [Google Scholar]
- Mond J. J., Feuerstein N., Finkelman F. D., Huang F., Huang K. P., Dennis G. B-lymphocyte activation mediated by anti-immunoglobulin antibody in the absence of protein kinase C. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8588–8592. doi: 10.1073/pnas.84.23.8588. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Noelle R. J., Roy M., Shepherd D. M., Stamenkovic I., Ledbetter J. A., Aruffo A. A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6550–6554. doi: 10.1073/pnas.89.14.6550. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Osborn L., Kunkel S., Nabel G. J. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336–2340. doi: 10.1073/pnas.86.7.2336. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parker D. C. T cell-dependent B cell activation. Annu Rev Immunol. 1993;11:331–360. doi: 10.1146/annurev.iy.11.040193.001555. [DOI] [PubMed] [Google Scholar]
- Pollok K. E., O'Brien V., Marshall L., Olson J. W., Noelle R. J., Snow E. C. The development of competence in resting B cells. The induction of cyclic AMP and ornithine decarboxylase activity after direct contact between B and T helper cells. J Immunol. 1991 Mar 1;146(5):1633–1641. [PubMed] [Google Scholar]
- Rooney J. W., Dubois P. M., Sibley C. H. Cross-linking of surface IgM activates NF-kappa B in B lymphocyte. Eur J Immunol. 1991 Dec;21(12):2993–2998. doi: 10.1002/eji.1830211214. [DOI] [PubMed] [Google Scholar]
- Rothstein T. L., Kolber D. L. Peritoneal B cells respond to phorbol esters in the absence of co-mitogen. J Immunol. 1988 May 1;140(9):2880–2885. [PubMed] [Google Scholar]
- 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]
- Shirakawa F., Chedid M., Suttles J., Pollok B. A., Mizel S. B. Interleukin 1 and cyclic AMP induce kappa immunoglobulin light-chain expression via activation of an NF-kappa B-like DNA-binding protein. Mol Cell Biol. 1989 Mar;9(3):959–964. doi: 10.1128/mcb.9.3.959. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shirakawa F., Mizel S. B. In vitro activation and nuclear translocation of NF-kappa B catalyzed by cyclic AMP-dependent protein kinase and protein kinase C. Mol Cell Biol. 1989 Jun;9(6):2424–2430. doi: 10.1128/mcb.9.6.2424. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tony H. P., Phillips N. E., Parker D. C. Role of membrane immunoglobulin (Ig) crosslinking in membrane Ig-mediated, major histocompatibility-restricted T cell-B cell cooperation. J Exp Med. 1985 Nov 1;162(5):1695–1708. doi: 10.1084/jem.162.5.1695. [DOI] [PMC free article] [PubMed] [Google Scholar]