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. 1989 Dec;68(4):526–531.

Regulation of resting and cycling human B lymphocytes via surface IgM and the accessory molecules interleukin-4, CD23 and CD40.

J Gordon 1, M J Millsum 1, L Flores-Romo 1, S Gillis 1
PMCID: PMC1385542  PMID: 2481643

Abstract

Experiments were designed in order to compare directly the ability of a new and potent monoclonal anti-mu chain antibody to initiate or maintain stimulation in resting and cycling B lymphocytes, respectively. Resting B cells could be stimulated by soluble anti-mu only in the presence of additional signals; these could be supplied by a high dose of phorbol ester or a combination of interleukin-4 (IL-4) and the CD40 antibody, G28-5. Immobilization of anti-mu not only increased the magnitude of the resting B-cell response but also diminished the co-factor requirements. The 'background' stimulation obtained when using a high concentration of immobilized anti-mu was unexpectedly reduced in the presence of IL-4 alone. The duration, but not the magnitude, of the IL-4 signal required for promoting optimal responses varied with the co-stimulation applied. Importantly, the threshold concentrations of soluble anti-mu needed to trigger the resting B cells were reduced upon the addition of each co-stimulant. With actively cycling B cells, both soluble and immobilized anti-mu were now capable of sustaining stimulation which could be prolonged on the addition of IL-4 and/or G28-5. In both resting and cycling populations, a strong correlation was noted between the magnitude of stimulation elicited when IL-4 was present and the release of the soluble CD23 molecule. Moreover, IL-4-promoted, but not other, stimulations could be augmented up to 10-fold by the inclusion of the CD23 antibody MHM6. Both the resting and cycling B-cell populations were found to secrete IgM in direct response to IL-4 and G28-5; this factor-driven production of IgM was differentially modulated by soluble and immobilized anti-mu in the two populations.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbas A. K., Klaus G. G. Inhibition of antibody production in plasmacytoma cells by antigen. Eur J Immunol. 1977 Oct;7(10):667–674. doi: 10.1002/eji.1830071003. [DOI] [PubMed] [Google Scholar]
  2. Aston R., Cowden W. B., Ada G. L. Antibody-mediated enhancement of hormone activity. Mol Immunol. 1989 May;26(5):435–446. doi: 10.1016/0161-5890(89)90103-x. [DOI] [PubMed] [Google Scholar]
  3. Bonvini E., Ruscetti F. W., Ponzoni M., Hoffman T., Farrar W. L. Interleukin 2 rapidly stimulates synthesis and breakdown of polyphosphoinositides in interleukin 2-dependent, murine T-cell lines. J Biol Chem. 1987 Mar 25;262(9):4160–4164. [PubMed] [Google Scholar]
  4. Cairns J., Flores-Romo L., Millsum M. J., Guy G. R., Gillis S., Ledbetter J. A., Gordon J. Soluble CD23 is released by B lymphocytes cycling in response to interleukin 4 and anti-Bp50 (CDw40). Eur J Immunol. 1988 Mar;18(3):349–353. doi: 10.1002/eji.1830180305. [DOI] [PubMed] [Google Scholar]
  5. Crow M. K., Jover J. A., Friedman S. M. Direct T helper-B cell interactions induce an early B cell activation antigen. J Exp Med. 1986 Nov 1;164(5):1760–1772. doi: 10.1084/jem.164.5.1760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Delespesse G., Sarfati M., Hofstetter H. Human IgE-binding factors. Immunol Today. 1989 May;10(5):159–164. doi: 10.1016/0167-5699(89)90173-4. [DOI] [PubMed] [Google Scholar]
  7. Flores-Romo L., Foster D., Guy G. R., Gordon J. Phorbol ester and calcium ionophore are sufficient to promote cell replication in cultures of quiescent human B lymphocytes. Immunology. 1989 Feb;66(2):228–232. [PMC free article] [PubMed] [Google Scholar]
  8. Gordon J., Cairns J. A., Millsum M. J., Gillis S., Guy G. R. Interleukin 4 and soluble CD23 as progression factors for human B lymphocytes: analysis of their interactions with agonists of the phosphoinositide "dual pathway" of signalling. Eur J Immunol. 1988 Oct;18(10):1561–1565. doi: 10.1002/eji.1830181014. [DOI] [PubMed] [Google Scholar]
  9. Gordon J., Flores-Romo L., Cairns J. A., Millsum M. J., Lane P. J., Johnson G. D., MacLennan I. C. CD23: a multi-functional receptor/lymphokine? Immunol Today. 1989 May;10(5):153–157. doi: 10.1016/0167-5699(89)90171-0. [DOI] [PubMed] [Google Scholar]
  10. Gordon J., Millsum M. J., Guy G. R., Ledbetter J. A. Resting B lymphocytes can be triggered directly through the CDw40 (Bp50) antigen. A comparison with IL-4-mediated signaling. J Immunol. 1988 Mar 1;140(5):1425–1430. [PubMed] [Google Scholar]
  11. Gordon J., Rowe M., Walker L., Guy G. Ligation of the CD23,p45 (BLAST-2,EBVCS) antigen triggers the cell-cycle progression of activated B lymphocytes. Eur J Immunol. 1986 Sep;16(9):1075–1080. doi: 10.1002/eji.1830160908. [DOI] [PubMed] [Google Scholar]
  12. Guy G. R., Bunce C. M., Gordon J., Michell R. H., Brown G. A combination of calcium ionophore and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulates the growth of purified resting B cells. Scand J Immunol. 1985 Nov;22(5):591–596. doi: 10.1111/j.1365-3083.1985.tb01919.x. [DOI] [PubMed] [Google Scholar]
  13. Jelinek D. F., Lipsky P. E. Inhibitory influence of IL-4 on human B cell responsiveness. J Immunol. 1988 Jul 1;141(1):164–173. [PubMed] [Google Scholar]
  14. MacLennan I. C., Gray D. Antigen-driven selection of virgin and memory B cells. Immunol Rev. 1986 Jun;91:61–85. doi: 10.1111/j.1600-065x.1986.tb01484.x. [DOI] [PubMed] [Google Scholar]
  15. Mizuguchi J., Beaven M. A., Li J. H., Paul W. E. Phorbol myristate acetate inhibits anti-IgM-mediated signaling in resting B cells. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4474–4478. doi: 10.1073/pnas.83.12.4474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Parker D. C. Stimulation of mouse lymphocytes by insoluble anti-mouse immunoglobulin. Nature. 1975 Nov 27;258(5533):361–363. doi: 10.1038/258361a0. [DOI] [PubMed] [Google Scholar]
  17. Paul W. E., Ohara J. B-cell stimulatory factor-1/interleukin 4. Annu Rev Immunol. 1987;5:429–459. doi: 10.1146/annurev.iy.05.040187.002241. [DOI] [PubMed] [Google Scholar]
  18. Rudich S. M., Winchester R., Mongini P. K. Human B cell activation. Evidence for diverse signals provided by various monoclonal anti-IgM antibodies. J Exp Med. 1985 Oct 1;162(4):1236–1255. doi: 10.1084/jem.162.4.1236. [DOI] [PMC free article] [PubMed] [Google Scholar]

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