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. 1979 Dec 1;150(6):1339–1350. doi: 10.1084/jem.150.6.1339

The purified protein derivative of turberculin, a B-cell mitogen that distinguishes in its action resting, small B cells from activated B- cell blasts

PMCID: PMC2185729  PMID: 315990

Abstract

The purified protein derivative of tuberculin (PPD tuberculin) stimulates approximately one of two lipopolysaccharide (LPS)-activated B-cell blasts of C57BL/6J nu/nu spleen cells to continued clonal growth and maturation to IgM and IgG secretion. It alwo stimulates background, in vivo-activated large cells of normal C57BL/6J nu/nu spleen to growth and Ig secretion, at a frequency of approximately 1 of 100 large spleen cells. PPD tuberculin, therefore, is a polyclonal B-cell activator for B-cell blasts. Many single murine splenic B cells (approximately 50%) appear to have reactivities, and therefore probably receptors, for LPS and PPD tuberculin. PPD tuberculin does not stimulate small, resting B cells to growth as measured by the number of cells in culture and by thymidine uptake. However, it stimulates approximately one-fourth of all spleen cells to blast transformation. The large-size blast cells secrete IgM and, therefore, form plaques in the protein A plaque assay. IgG-secreting, plaque-forming cells develop at later stages of stimulation, indicating that the switch from IgM to IgG may occur without division in single, stimulated B cells. Stimulation of resting B cells to maturation by PPD tuberculin is polyclonal. Thus, approximately 1 in 10(2) IgM-secreting plaque-forming cells form plaques with trinitrophenyl-substituted sheep erythrocytes, 1 in 450 do so with horse erythrocytes, and 1 in 10(3) with sheep erythrocytes. Furthermore, the number of Ig-secreting cells developing from small, resting cells without growth in cultures with or without filler thymus cells suggests polyclonal activation by PPD tuberculin to maturation only of at least one out of four small, splenic B cells.

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Selected References

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  1. Andersson J., Bullock W. W., Melchers F. Inhibition of mitogenic stimulation of mouse lymphocytes by anti-mouse immunoglobulin antibodies. I. Mode of action. Eur J Immunol. 1974 Nov;4(11):715–722. doi: 10.1002/eji.1830041103. [DOI] [PubMed] [Google Scholar]
  2. Andersson J., Coutinho A., Lernhardt W., Melchers F. Clonal growth and maturation to immunoglobulin secretion in vitro of every growth-inducible B lymphocyte. Cell. 1977 Jan;10(1):27–34. doi: 10.1016/0092-8674(77)90136-2. [DOI] [PubMed] [Google Scholar]
  3. Andersson J., Coutinho A., Melchers F. Frequencies of mitogen-reactive B cells in the mouse. I. Distribution in different lymphoid organs from different inbred strains of mice at different ages. J Exp Med. 1977 Jun 1;145(6):1511–1519. doi: 10.1084/jem.145.6.1511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Andersson J., Coutinho A., Melchers F. Frequencies of mitogen-reactive B cells in the mouse. II. Frequencies of B cells producing antibodies which lyse sheep or horse erythrocytes, and trinitrophenylated or nitroiodophenylated sheep erythrocytes. J Exp Med. 1977 Jun 1;145(6):1520–1530. doi: 10.1084/jem.145.6.1520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Andersson J., Coutinho A., Melchers F. Mitogen-activated B-cell blasts reactive to more than one mitogen. J Exp Med. 1979 Mar 1;149(3):553–564. doi: 10.1084/jem.149.3.553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Andersson J., Coutinho A., Melchers F. The switch from IgM to IgG secretion in single mitogen-stimulated B-cell clones. J Exp Med. 1978 Jun 1;147(6):1744–1754. doi: 10.1084/jem.147.6.1744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Andersson J., Lafleur L., Melchers IgM in bone marrow-derived lymphocytes. Synthesis, surface deposition, turnover and carbohydrate composition in unstimulated mouse B cells. Eur J Immunol. 1974 Mar;4(3):170–180. doi: 10.1002/eji.1830040305. [DOI] [PubMed] [Google Scholar]
  8. Andersson J., Melchers F. Maturation of mitogen-activated bone marrow-derived lymphocytes in the absence of proliferation. Eur J Immunol. 1974 Aug;4(8):533–539. doi: 10.1002/eji.1830040803. [DOI] [PubMed] [Google Scholar]
  9. Andersson J., Sjöberg O., Möller G. Induction of immunoglobulin and antibody synthesis in vitro by lipopolysaccharides. Eur J Immunol. 1972 Aug;2(4):349–353. doi: 10.1002/eji.1830020410. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Coutinho A., Möller G., Anderson J., Bullock W. W. In vitro activation of mouse lymphocytes in serum-free medium: effect of T and B cell mitogens on proliferation and antibody synthesis. Eur J Immunol. 1973 May;3(5):299–306. doi: 10.1002/eji.1830030509. [DOI] [PubMed] [Google Scholar]
  12. Fu S. M., Chiorazzi N., Kunkel H. G., Halper J. P., Harris S. R. Induction of in vitro differentiation and immunoglobulin synthesis of human leukemic B lymphocytes. J Exp Med. 1978 Dec 1;148(6):1570–1578. doi: 10.1084/jem.148.6.1570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gronowicz E., Coutinho A. Heterogeneity of B cells: direct evidence of selective triggering of distinct subpopulations by polyclonal activators. Scand J Immunol. 1976;5(1-2):55–69. doi: 10.1111/j.1365-3083.1976.tb02992.x. [DOI] [PubMed] [Google Scholar]
  14. Gronowicz E., Coutinho A., Melchers F. A plaque assay for all cells secreting Ig of a given type or class. Eur J Immunol. 1976 Aug;6(8):588–590. doi: 10.1002/eji.1830060812. [DOI] [PubMed] [Google Scholar]
  15. Gronowicz E., Coutinho A., Möller G. Differentiation of B cells: sequential appearance of responsiveness to polyclonal activators. Scand J Immunol. 1974;3(4):413–421. doi: 10.1111/j.1365-3083.1974.tb01274.x. [DOI] [PubMed] [Google Scholar]
  16. Gronowicz E., Coutinho A. Selective triggering of B cell subpopulations by mitogens. Eur J Immunol. 1974 Nov;4(11):771–776. doi: 10.1002/eji.1830041113. [DOI] [PubMed] [Google Scholar]
  17. Iscove N. N., Melchers F. Complete replacement of serum by albumin, transferrin, and soybean lipid in cultures of lipopolysaccharide-reactive B lymphocytes. J Exp Med. 1978 Mar 1;147(3):923–933. doi: 10.1084/jem.147.3.923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Katz D. H., Skidmore B. J., Katz L. R., Bogowitz C. A. Adaptive differentiation of murine lymphocytes. I. Both T and B lymphocytes differentiating in F1 transplanted to parental chimeras manifest preferential cooperative activity for partner lymphocytes derived from the same parental type corresponding to the chimeric host. J Exp Med. 1978 Sep 1;148(3):727–745. doi: 10.1084/jem.148.3.727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kincade P. W., Ralph P., Moore M. A. Growth of B-lymphocytes clones in semisolid culture is mitogen dependent. J Exp Med. 1976 May 1;143(5):1265–1270. doi: 10.1084/jem.143.5.1265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kishimoto T., Miyake T., Nishizawa Y., Watanabe T., Yamamura Y. Triggering mechanism of B lymphocytes. I. Effect of anti-immunoglobulin and enhancing soluble factor on differentiation and proliferation of B cells. J Immunol. 1975 Nov;115(5):1179–1184. [PubMed] [Google Scholar]
  21. Melchers F., Andersson J. The kinectics of proliferation and maturation of mitogen-activated bone marrow-derived lymphocytes. Eur J Immunol. 1974 Oct;4(10):687–691. doi: 10.1002/eji.1830041010. [DOI] [PubMed] [Google Scholar]
  22. Melchers F., Braun V., Galanos C. The lipoprotein of the outer membrane of Escherichia coli: a B-lymphocyte mitogen. J Exp Med. 1975 Aug 1;142(2):473–482. doi: 10.1084/jem.142.2.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Melchers F., Coutinho A., Heinrich G., Andersson J. Continuous growth of mitogen-reactive B lymphocytes. Scand J Immunol. 1975;4(8):853–858. doi: 10.1111/j.1365-3083.1975.tb03728.x. [DOI] [PubMed] [Google Scholar]
  24. Metcalf D. Role of mercaptoethanol and endotoxin in stimulating B lymphocyte colony formation in vitro. J Immunol. 1976 Mar;116(3):635–638. [PubMed] [Google Scholar]
  25. Miller R. G., Phillips R. A. Separation of cells by velocity sedimentation. J Cell Physiol. 1969 Jun;73(3):191–201. doi: 10.1002/jcp.1040730305. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Sprent J. Role of H-2 gene products in the function of T helper cells from normal and chimeric mice in vivo. Immunol Rev. 1978;42:108–137. doi: 10.1111/j.1600-065x.1978.tb00260.x. [DOI] [PubMed] [Google Scholar]
  28. Sultzer B. M., Nilsson B. S. PPD tuberculin--a B-cell mitogen. Nat New Biol. 1972 Dec 13;240(102):198–200. doi: 10.1038/newbio240198a0. [DOI] [PubMed] [Google Scholar]

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