Abstract
Populations of murine peritoneal B-1 and splenic B-2 cells, highly purified by negative selection techniques, were used to demonstrate that B-1 cells completely fail to enter cell cycle in response to surface immunoglobulin M (sIgM) crosslinking without any decrease in cell number or viability. This failure of B-1 cell responsiveness appears to represent a specific defect in sIgM-derived signaling inasmuch as stimulation to enter S phase occurs normally in response to activated and fixed T cells, and to lipopolysaccharide (LPS). The level at which sIgM signaling fails was determined by evaluating the nuclear expression of the transcription factor complex, NF-kappa B, whose sIgM- mediated induction in B-2 cells is dependent on protein kinase C (PKC) activation but is independent of protein synthesis. There was no induction of nuclear NF-kappa B in B-1 cells stimulated by sIgM crosslinking, although NF-kappa B was stimulated by phorbol myristate acetate and by LPS. In contrast, NF-kappa B was induced in B-2 cells by all three stimuli. Thus, in B-1 cells, the sIgM-mediated induction of a transcription factor that is substantially stimulated by anti-IgM in B- 2 cells is blocked. However, all sIgM-derived signaling in B-1 cells was not impaired inasmuch as anti-IgM increased I-A antigen expression. These results strongly suggest that sIgM receptor-mediated signaling in B-1 cells is interrupted early in the signal transduction pathway, at a point proximal to the activation of PKC. These results further demonstrate that transcription factor induction can be used to analyze the level at which receptor-mediated signaling is blocked.
Full Text
The Full Text of this article is available as a PDF (854.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Cong Y. Z., Rabin E., Wortis H. H. Treatment of murine CD5- B cells with anti-Ig, but not LPS, induces surface CD5: two B-cell activation pathways. Int Immunol. 1991 May;3(5):467–476. doi: 10.1093/intimm/3.5.467. [DOI] [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]
- Kawakami K., Parker D. C. Differences between T helper cell type I (Th1) and Th2 cell lines in signalling pathways for induction of contact-dependent T cell help. Eur J Immunol. 1992 Jan;22(1):85–93. doi: 10.1002/eji.1830220114. [DOI] [PubMed] [Google Scholar]
- Kipps T. J. The CD5 B cell. Adv Immunol. 1989;47:117–185. doi: 10.1016/s0065-2776(08)60663-x. [DOI] [PubMed] [Google Scholar]
- Kolber D. L., Shultz L. D., Rothstein T. L. Phorbol ester responsiveness of murine Ly-1-lineage B cells from normal and viable motheaten mutant mice. Eur J Immunol. 1991 Mar;21(3):721–729. doi: 10.1002/eji.1830210327. [DOI] [PubMed] [Google Scholar]
- Liou L. B., Warner G. L., Scott D. W. Can peritoneal B cells be rendered unresponsive? Int Immunol. 1992 Jan;4(1):15–21. doi: 10.1093/intimm/4.1.15. [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]
- Murphy T. P., Kolber D. L., Rothstein T. L. Elevated expression of Pgp-1 (Ly-24) by murine peritoneal B lymphocytes. Eur J Immunol. 1990 May;20(5):1137–1142. doi: 10.1002/eji.1830200529. [DOI] [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]
- O'Garra A., Howard M. Cytokines and Ly-1 (B1) B cells. Int Rev Immunol. 1992;8(2-3):219–234. doi: 10.3109/08830189209055575. [DOI] [PubMed] [Google Scholar]
- Plater-Zyberk C., Brown C. M., Andrew E. M., Maini R. N. CD5+B in rheumatoid arthritis. Ann N Y Acad Sci. 1992 May 4;651:540–550. doi: 10.1111/j.1749-6632.1992.tb24660.x. [DOI] [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. Anti-Ig antibody inhibits the phorbol ester-induced stimulation of peritoneal B cells. J Immunol. 1988 Dec 15;141(12):4089–4093. [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. Polyreactive low-affinity IgM antibodies produced by CD5+ B cells. Immunol Today. 1990 May;11(5):152–152. doi: 10.1016/0167-5699(90)90062-e. [DOI] [PubMed] [Google Scholar]