Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1978 Dec 1;148(6):1628–1643. doi: 10.1084/jem.148.6.1628

Activation of mouse lymphocytes by anti-immunoglobulin. II. A thymus- independent response by a mature subset of B lymphocytes

PMCID: PMC2185118  PMID: 102729

Abstract

Mouse spleen cells can be stimulated to proliferate in vitro by purified anti-mu or anti-gamma,kappa antibodies. These responses can be obtained in cell populations bearing membrane immunoglobulin (Ig), purified by the fluorescence activated cell sorter (FACS), but they are not observed in FACS-purified Ig- cell populations. Furthermore, treatment of spleen cell populations with anti-Thy 1.2 and complement does not impair the response, nor does addition of nylon wool-purified T lymphocytes enhance it. These results indicate that B lymphocytes respond to anti-Ig and that their response does not require T cells. On the other hand, cells from athymic nude (nu/nu) mice respond slightly less well to anti-mu than do cells from heterozygous littermate (nu/+) controls; nu/nu cells are almost unresponsive to anti-gamm,kappa and addition of nylon wool-purified T cells from nu/+ controls does not restore the response. This suggests that T lymphocytes or the thymus may control the appearance of cells responsive to anti-gamma,kappa. Responsiveness of normal mice to anti-mu does not appear until 4 wk of age and does not reach maximum levels until 8 wk of age. Acquisition of full responsiveness to anti-gamma,kappa is even more delayed. This, together with the failure of mice with the CBA/N B-cell defect to respond to anti-Ig, suggests that cells stimulated to proliferate by anti-Ig are a mature subset of B cells. Depletion of adherent cells by Sephadex G-10 treatment or by treatment with carbonyl iron and exposure to a magnetic field does not diminish anti-mu or anti-gamma,kappa responses, suggesting that the responsiveness does not require the presence of macrophages. Thus, activation of B-cell proliferation by anti-Ig appears to be a T-cell independent, macrophage-independent process in which membrane Ig plays a direct role in signal generation.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. Adinolfi M., Gardner B., Giannelli F., McGuire M. Studies on human lymphocytes stimulated in vitro with anti-gamma and anti-mu antibodies. Experientia. 1967 Apr 15;23(4):271–272. doi: 10.1007/BF02135679. [DOI] [PubMed] [Google Scholar]
  2. Ahmed A., Scher I., Sharrow S. O., Smith A. H., Paul W. E., Sachs D. H., Sell K. W. B-lymphocyte heterogeneity: development and characterization of an alloantiserum which distinguishes B-lymphocyte differentiation alloantigens. J Exp Med. 1977 Jan 1;145(1):101–110. doi: 10.1084/jem.145.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Amsbaugh D. F., Hansen C. T., Prescott B., Stashak P. W., Barthold D. R., Baker P. J. Genetic control of the antibody response to type 3 pneumococcal polysaccharide in mice. I. Evidence that an X-linked gene plays a decisive role in determining responsiveness. J Exp Med. 1972 Oct 1;136(4):931–949. doi: 10.1084/jem.136.4.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barton M. A., Diener E. A new perspective on B cell triggering: control of the immune response by organizational changes in the lipid bilayer. Transplant Rev. 1975;23:5–22. doi: 10.1111/j.1600-065x.1975.tb00145.x. [DOI] [PubMed] [Google Scholar]
  5. Bona C., Damais C., Chedid L. Blastic transformtion of mouse spleen lymphocytes by a water-soluble mitogen extracted from Nocardia. Proc Natl Acad Sci U S A. 1974 May;71(5):1602–1606. doi: 10.1073/pnas.71.5.1602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bretscher P. A. The two signal model for b cell induction. Transplant Rev. 1975;23:37–48. doi: 10.1111/j.1600-065x.1975.tb00147.x. [DOI] [PubMed] [Google Scholar]
  7. Bretscher P., Cohn M. A theory of self-nonself discrimination. Science. 1970 Sep 11;169(3950):1042–1049. doi: 10.1126/science.169.3950.1042. [DOI] [PubMed] [Google Scholar]
  8. Coutinho A., Möller G. Editorial: Immune activation of B cells: evidence for 'one nonspecific triggering signal' not delivered by the Ig receptors. Scand J Immunol. 1974;3(2):133–146. [PubMed] [Google Scholar]
  9. Coutinho A., Möller G. Thymus-independent B-cell induction and paralysis. Adv Immunol. 1975;21:113–236. doi: 10.1016/s0065-2776(08)60220-5. [DOI] [PubMed] [Google Scholar]
  10. Coutinho A. The theory of the 'one nonspecific signal' model for b cell activation. Transplant Rev. 1975;23:49–65. doi: 10.1111/j.1600-065x.1975.tb00148.x. [DOI] [PubMed] [Google Scholar]
  11. Cowing C., Schwartz B. D., Dickler H. B. Macrophage Ia antigens. I. macrophage populations differ in their expression of Ia antigens. J Immunol. 1978 Feb;120(2):378–384. [PubMed] [Google Scholar]
  12. Daguillard F., Heiner D. C., Richter M., Rose B. The response of leucocytes of agammaglobulinaemia subjects to phythohaemagglutinin and anti-immunoglobulin antiserum. Clin Exp Immunol. 1969 Feb;4(2):203–211. [PMC free article] [PubMed] [Google Scholar]
  13. Davie J. M., Paul W. E. Role of T lymphocytes in the humoral immune response. I. Proliferation of B lymphocytes in thymus-deprived mice. J Immunol. 1974 Nov;113(5):1438–1445. [PubMed] [Google Scholar]
  14. Diener E., Feldmann M. Relationship between antigen and antibody-induced suppression of immunity. Transplant Rev. 1972;8:76–103. doi: 10.1111/j.1600-065x.1972.tb01565.x. [DOI] [PubMed] [Google Scholar]
  15. Dutton R. W. Separate signals for the initiation of proliferation and differentiation in the b cell response to antigen. Transplant Rev. 1975;23:66–77. doi: 10.1111/j.1600-065x.1975.tb00149.x. [DOI] [PubMed] [Google Scholar]
  16. Gausset P., Delespesse G., Hubert C., Kennes B., Govaerts A. In vitro response of subpopulations of human lymphocytes. II. DNA synthesis induced by anti-immunoglobulin antibodies. J Immunol. 1976 Feb;116(2):446–453. [PubMed] [Google Scholar]
  17. Gelfand M. C., Elfenbein G. J., Frank M. M., Paul W. E. Ontogeny of B lymphocytes. II. Relative rates of appearance of lymphocytes bearing surface immunoglobulin and complement receptors. J Exp Med. 1974 May 1;139(5):1125–1141. doi: 10.1084/jem.139.5.1125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Habu S., Raff M. C. Accessory cell dependence of lectin-induced proliferation of mouse T lymphocytes. Eur J Immunol. 1977 Jul;7(7):451–457. doi: 10.1002/eji.1830070710. [DOI] [PubMed] [Google Scholar]
  19. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  20. Kirchner H., Oppenheim J. J. Stimulation of chicken lymphocytes in a serum-free medium. Cell Immunol. 1972 Apr;3(4):695–699. doi: 10.1016/0008-8749(72)90131-1. [DOI] [PubMed] [Google Scholar]
  21. Kishimoto T., Ishizaka K. Regulation of antibody response in vitro. IX. Induction of secondary anti-hapten IgG antibody response by anti-immunoglobulin and enhancing soluble factor. J Immunol. 1975 Feb;114(2 Pt 1):585–591. [PubMed] [Google Scholar]
  22. Maino V. C., Hayman M. J., Crumpton M. J. Relationship between enhanced turnover of phosphatidylinositol and lymphocyte activation by mitogens. Biochem J. 1975 Jan;146(1):247–252. doi: 10.1042/bj1460247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Oppenheim J. J., Rogentine G. N., Terry W. D. The transformation of human lymphocytes by monkey antisera to human immunoglobulins. Immunology. 1969 Jan;16(1):123–138. [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Reif A. E., Allen J. M. Mouse thymic iso-antigens. Nature. 1966 Jan 29;209(5022):521–523. doi: 10.1038/209521b0. [DOI] [PubMed] [Google Scholar]
  27. SELL S., GELL P. G. STUDIES ON RABBIT LYMPHOCYTES IN VITRO. I. STIMULATION OF BLAST TRANSFORMATION WITH AN ANTIALLOTYPE SERUM. J Exp Med. 1965 Aug 1;122:423–440. doi: 10.1084/jem.122.2.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Scher I., Sharrow S. O., Paul W. E. X-linked B-lymphocyte defect in CBA/N mice. III. Abnormal development of B-lymphocyte populations defined by their density of surface immunoglobulin. J Exp Med. 1976 Aug 1;144(2):507–518. doi: 10.1084/jem.144.2.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Scher I., Sharrow S. O., Wistar R., Jr, Asofsky R., Paul W. E. B-lymphocyte heterogeneity: ontogenetic development and organ distribution of B-lymphocyte populations defined by their density of surface immunoglobulin. J Exp Med. 1976 Aug 1;144(2):494–506. doi: 10.1084/jem.144.2.494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Scher I., Steinberg A. D., Berning A. K., Paul W. E. X-linked B-lymphocyte immune defect in CBA/N mice. II. Studies of the mechanisms underlying the immune defect. J Exp Med. 1975 Sep 1;142(3):637–650. doi: 10.1084/jem.142.3.637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Schrader J. W. Mechanism of activation of the bone marrow-derived lymphocyte. 3. A distinction between a macrophage-produced triggering signal and the amplifying effect on triggered B lymphocytes of allogeneic interactions. J Exp Med. 1973 Dec 1;138(6):1466–1480. doi: 10.1084/jem.138.6.1466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schreiner G. F., Unanue E. R. Membrane and cytoplasmic changes in B lymphocytes induced by ligand-surface immunoglobulin interaction. Adv Immunol. 1976;24:37–165. doi: 10.1016/s0065-2776(08)60329-6. [DOI] [PubMed] [Google Scholar]
  33. Sieckmann D. G., Asofsky R., Mosier D. E., Zitron I. M., Paul W. E. Activation of mouse lymphocytes by anti-immunoglobulin. I. Parameters of the proliferative response. J Exp Med. 1978 Mar 1;147(3):814–829. doi: 10.1084/jem.147.3.814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sjöberg O., Andersson J., Möller G. Requirement for adherent cells in the primary and secondary immune response in vitro. Eur J Immunol. 1972 Apr;2(2):123–126. doi: 10.1002/eji.1830020206. [DOI] [PubMed] [Google Scholar]
  35. Skamene E., Ivanyi J. Lymphocyte transformation by H-chain specific anti-immunoglobulin sera. Nature. 1969 Feb 15;221(5181):681–682. doi: 10.1038/221681a0. [DOI] [PubMed] [Google Scholar]
  36. Warner N. L. Membrane immunoglobulins and antigen receptors on B and T lymphocytes. Adv Immunol. 1974;19(0):67–216. doi: 10.1016/s0065-2776(08)60252-7. [DOI] [PubMed] [Google Scholar]
  37. Weiner H. L., Moorhead J. W., Claman H. N. Anti-immunoglobulin stimulation of murine lymphocytes. I. Age dependency of the proliferative response. J Immunol. 1976 Jun;116(6):1656–1661. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES