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. 1980 Feb 1;151(2):446–466. doi: 10.1084/jem.151.2.446

Splenic immunoglobulin-secreting cells and their regulation in autoimmune mice

PMCID: PMC2185774  PMID: 6444324

Abstract

We have investigated in vitro the magnitude, nature, and regulation of spontaneous and mitogen-induced Ig secretion by splenic lymphocytes from several autoimmune murine strains (NZB, NZB X W, MRL/l BXSB) and appropriate, normal mice. All autoimmune strains had increased numbers of mature splenic B lymphocytes, which secreted and/or contained Ig, compared to age-matched normal strains. In NZB and NZB X W mice, the high frequency of mature B cells was apparent early in life, whereas in MRL/l and BXSB mice it was first noted shortly before the clinical onset of disease. Spleen cells from young autoimmune mice of all four strains secreted predominantly IgM, but with aging and the appearance of disease, the cells switched to IgG secretion predominantly. In contrast, spleen cells from normal mice were predominantly IgM, but with aging and the appearance of disease, the cells switched to IgG secretion predominantly. In contrast, spleen cells from normal mice were predominantly IgM secretors throughout the animals' lives. Approximately 15% of the total Ig-secreting cells in older NZB, NZB X W, and MRL mice were committed to secretion of anti-ssDNA antibodies. In both autoimmune and normal spleen cells, the B-cell population alone contained fewer secreting cells than the total lymphocyte population, indicating that T cells were required to achieve maximal levels of plaque-forming cells. Spleen cells of NZB and NZB X W mice had a greater response to lipopolysaccharide (LPS) than other autoimmune and normal strains. Responsiveness to LPS, as measured by the frequency of induced Ig-secreting cells, was considerably diminished with age and onset of disease in all autoimmune but not in normal strains. LPS- induced Ig secretion by B cells of autoimmune and normal mice was subject to regulation by splenic T cells. No significant differences were observed between concanavalin-A (Con A) stimulated spleen cells from young and older autoimmune mice and normal control strains in effectively suppressing spontaneous and LPS-induced Ig secretion. Moreover, B cells from autoimmune mice and from normal strains were equally receptive to Con A-induced suppressor signals. T cells from young and older NZB and BXSB mice added to a standard number of B cells from syngeneic young mice provided equal help in enhancing LPS-induced Ig secretion, and this help in turn was equivalent to that provided by T cells from normal mice of the same H-2 haplotype. The exception was the MRL/l strain; T cells from older animals provided considerably more help than T cells from young MRL/l or T cells from young and older H-2- compatible normal mice.

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Selected References

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

  1. Allison A. C., Denman A. M., Barnes R. D. Cooperating and controlling functions of thymus-derived lymphocytes in relation to autoimmunity. Lancet. 1971 Jul 17;2(7716):135–140. doi: 10.1016/s0140-6736(71)92306-3. [DOI] [PubMed] [Google Scholar]
  2. Andrews B. S., Eisenberg R. A., Theofilopoulos A. N., Izui S., Wilson C. B., McConahey P. J., Murphy E. D., Roths J. B., Dixon F. J. Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med. 1978 Nov 1;148(5):1198–1215. doi: 10.1084/jem.148.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bell D. A., Clark C., Blomgren S. E., Vaughan J. H. Anti DNA antibody production by lymphoid cells of NZB-W mice and human systemic lupus erythematosus (SLE). Clin Immunol Immunopathol. 1973 Apr;1(3):293–303. doi: 10.1016/0090-1229(73)90046-9. [DOI] [PubMed] [Google Scholar]
  4. Bonner W. A., Hulett H. R., Sweet R. G., Herzenberg L. A. Fluorescence activated cell sorting. Rev Sci Instrum. 1972 Mar;43(3):404–409. doi: 10.1063/1.1685647. [DOI] [PubMed] [Google Scholar]
  5. Bourgois A., Kitajima K., Hunter I. R., Askonas B. A. Surface immunoglobulins of lipopolysaccharide-stimulated spleen cells. The behavior of IgM, IgD and IgG. Eur J Immunol. 1977 Mar;7(3):151–153. doi: 10.1002/eji.1830070307. [DOI] [PubMed] [Google Scholar]
  6. Cantor H., McVay-Boudreau L., Hugenberger J., Naidorf K., Shen F. W., Gershon R. K. Immunoregulatory circuits among T-cell sets. II. Physiologic role of feedback inhibition in vivo: absence in NZB mice. J Exp Med. 1978 Apr 1;147(4):1116–1125. doi: 10.1084/jem.147.4.1116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cohen P. L., Ziff M. Abnormal polyclonal B cell activation in NZB/NZW F1 mice. J Immunol. 1977 Oct;119(4):1534–1537. [PubMed] [Google Scholar]
  8. Cohen P., Ziff M., Vitetta E. S. Characterization of a B cell defect in the NZB mouse manifested by an increased ratio of surface IgM to IgD. J Immunol. 1978 Sep;121(3):973–977. [PubMed] [Google Scholar]
  9. Creighton W. D., Katz D. H., Dixon F. J. Antigen-specific immunocompetency, B cell function, and regulatory helper and suppressor T cell activities in spontaneously autoimmune mice. J Immunol. 1979 Dec;123(6):2627–2636. [PubMed] [Google Scholar]
  10. Dutton R. W. Inhibitory and stimulatory effects of concanavalin A on the response of mouse spleen cell suspensions to antigen. I. Characterization of the inhibitory cell activity. J Exp Med. 1972 Dec 1;136(6):1445–1460. doi: 10.1084/jem.136.6.1445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gershwin M. E., Castles J. J., Ikeda R. M., Erickson K., Montero J. Studies of congenitally immunologic mutant New Zealand mice. I. Autoimmune features of hereditarily asplenic (Dh/+) NZB mice; reduction of naturally occurring thymocytotoxic antibody and normal suppressor function. J Immunol. 1979 Feb;122(2):710–717. [PubMed] [Google Scholar]
  12. Goodman M. G., Weigle W. O. T cell regulation of polyclonal B cell responsiveness. I. Helper effects of T cells. J Immunol. 1979 Jun;122(6):2548–2553. [PubMed] [Google Scholar]
  13. Hardin J. A., Chused T. M., Steinberg A. D. Supressor cells in the graft vs host reaction. J Immunol. 1973 Aug;111(2):650–651. [PubMed] [Google Scholar]
  14. Hoffman A. A., Harbeck R. J. Immunoregulation in New Zealand mice. I. Failure of the transfer of syngeneic spleen or thymus cells to influence the natural disease in New Zealand mice. Arthritis Rheum. 1979 Apr;22(4):412–418. doi: 10.1002/art.1780220416. [DOI] [PubMed] [Google Scholar]
  15. Izui S., McConahey P. J., Dixon F. J. Increased spontaneous polyclonal activation of B lymphocytes in mice with spontaneous autoimmune disease. J Immunol. 1978 Dec;121(6):2213–2219. [PubMed] [Google Scholar]
  16. Katz D. H., Osborne D. P., Jr The allogeneic effect in inbred mice. II. Establishment of the cellular interactions required for enhancement of antibody production by the graft-versus-host reaction. J Exp Med. 1972 Sep 1;136(3):455–465. doi: 10.1084/jem.136.3.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kenny J. J., Kessler S. W., Ahmed A., Ashman R. F., Scher I. Changes in surface immunoglobulin isotypes on purified antigen-binding cells after antigenic stimulation. J Immunol. 1979 May;122(5):2037–2044. [PubMed] [Google Scholar]
  18. Kofler R., Wick G. Some methodologic aspects of the chromium chloride method for coupling antigen to erythrocytes. J Immunol Methods. 1977;16(3):201–209. doi: 10.1016/0022-1759(77)90198-3. [DOI] [PubMed] [Google Scholar]
  19. Kysela S., Steinberg A. D. Increased survival of NZB-W mice given multiple syngeneic young thymus grafts. Clin Immunol Immunopathol. 1973 Nov;2(1):133–136. doi: 10.1016/0090-1229(73)90043-3. [DOI] [PubMed] [Google Scholar]
  20. Manny N., Datta S. K., Schwartz R. S. Synthesis of IgM by cells of NZB and SWR mice and their crosses. J Immunol. 1979 Apr;122(4):1220–1227. [PubMed] [Google Scholar]
  21. McHugh Y. E., Bonavida B. Autoreactive antibody-forming cells directed against thymocytes and thymus-derived lymphocytes. J Immunol. 1978 Sep;121(3):1090–1095. [PubMed] [Google Scholar]
  22. Molinaro G. A., Dray S. Antibody coated erythrocytes as a manifold probe for antigens. Nature. 1974 Apr 5;248(448):515–517. doi: 10.1038/248515a0. [DOI] [PubMed] [Google Scholar]
  23. Moutsopoulos H. M., Boehm-Truitt M., Kassan S. S., Chused T. M. Demonstration of activation of B lymphocytes in New Zealand black mice at birth by an immunoradiometric assay for murine IgM. J Immunol. 1977 Nov;119(5):1639–1644. [PubMed] [Google Scholar]
  24. Nakajima P. B., Datta S. K., Schwartz R. S., Huber B. T. Localization of spontaneously hyperactive B cells of NZB mice to a specific B cell subset. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4613–4616. doi: 10.1073/pnas.76.9.4613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Norcross M. A., Smith R. T. Regulation of B-cell proliferative responses to lipopolysaccharide by a subclass of thymus T cells. J Exp Med. 1977 May 1;145(5):1299–1315. doi: 10.1084/jem.145.5.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Papoian R., Pillarisetty R., Talal N. Immunological regulation of spontaneous antibodies to DNA and RNA. II. Sequential switch from IgM to IgG in NZB/NZW F1 mice. Immunology. 1977 Jan;32(1):75–79. [PMC free article] [PubMed] [Google Scholar]
  27. Primi D., Hammarström L., Smith C. I. Genetic control of lymphocyte suppression. I. Lack of suppression in aged NZB mice is due to a B cell defect. J Immunol. 1978 Dec;121(6):2241–2243. [PubMed] [Google Scholar]
  28. Rich R. R., Pierce C. W. Biological expressions of lymphocyte activation : I. Effects of phytomitogens on antibody synthesis in vitro. J Exp Med. 1973 Jan 31;137(2):205–223. doi: 10.1084/jem.137.2.205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Roder J. C., Bell D. A., Singhal S. K. Loss of self-tolerance to single-stranded deoxyribonucleic acid (sDNA) in vitro. J Immunol. 1978 Jul;121(1):29–37. [PubMed] [Google Scholar]
  30. Roder J. C., Bell D. A., Singhal S. K. Regulation of the autoimmune plaque-forming cell response to single-strand DNA (sDNA) in vitro. J Immunol. 1978 Jul;121(1):38–43. [PubMed] [Google Scholar]
  31. Roder J. C., Bell D. A., Singhal S. K. Regulation of the immune response in autoimmune NZB/NZW F1 mice. I. The spontaneous generation of splenic suppressor cells. Cell Immunol. 1977 Mar 15;29(2):272–284. doi: 10.1016/0008-8749(77)90322-7. [DOI] [PubMed] [Google Scholar]
  32. Sawada S., Talal N. Characteristics of in vitro production of antibodies to DNA in normal and autoimmune mice. J Immunol. 1979 Jun;122(6):2309–2313. [PubMed] [Google Scholar]
  33. Strelkauskas A. J., Wilson B. S., Callery R. T., Chess L., Schlossman S. F. T-cell regulation of human peripheral blood B-cells responsiveness. J Exp Med. 1977 Dec 1;146(6):1765–1772. doi: 10.1084/jem.146.6.1765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Taurog J. D., Moutsopoulos H. M., Rosenberg Y. J., Chused T. M., Steinberg A. D. CBA/N X-linked B-cell defect prevents NZB B-cell hyperactivity in F1 mice. J Exp Med. 1979 Jul 1;150(1):31–43. doi: 10.1084/jem.150.1.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Theofilopoulos A. N., Eisenberg R. A., Bourdon M., Crowell J. S., Jr, Dixon F. J. Distribution of lymphocytes identified by surface markers in murine strains with systemic lupus erythematosus-like syndromes. J Exp Med. 1979 Feb 1;149(2):516–534. doi: 10.1084/jem.149.2.516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Zan-Bar I., Strober S., Vitetta E. S. The relationship between surface immunoglobulin isotype and immune function of murine B lymphocytes. I. Surface immunoglobulin isotypes on primed B cells in the spleen. J Exp Med. 1977 May 1;145(5):1188–1205. doi: 10.1084/jem.145.5.1188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Zan-Bar I., Vitetta E. S., Strober S. The relationship between surface immunoglobulin isotype and immune function of murine B lymphocytes II. Surface immunoglobulin isotopes on unprimed B cells in the spleen. J Exp Med. 1977 May 1;145(5):1206–1215. doi: 10.1084/jem.145.5.1206. [DOI] [PMC free article] [PubMed] [Google Scholar]

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