Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1982;1(10):1251–1257. doi: 10.1002/j.1460-2075.1982.tb00021.x

Intraclonal diversification in immunoglobulin isotype secretion: an analysis of switch probabilities.

A Coutinho, L Forni
PMCID: PMC553197  PMID: 6765193

Abstract

The production of all immunoglobulin isotypes except IgD was studied in a large number of single lipopolysaccharide (LPS)-reactive B cell clones. The majority, but not all, of the IgM-producing clones were found to secrete one or more other isotypes. IgG3 and IgG2b were most frequently found while IgA secretion was extremely rare. Many clones produced all four IgG subclasses and the statistical analysis of the data indicates, with a high degree of significance, that single clonal precursors give rise to progenies producing multiple isotypes. By assuming that intraclonal diversification follows the C-gene order in chromosome 12, the absolute switch probabilities of normal, unprimed LPS-reactive B cells can be calculated. The multi-potentiality of C-gene expression was further analyzed at the single cell level: a sizeable fraction of all activated B cells express two different IgG isotypes in the membrane-bound form, indicating consecutive switch events. In contrast, the majority of IgE and IgA secreting cells appear to switch directly from IgM. These results might reflect the functional relevance of S-region homologies in the control of C-gene expression.

Full text

PDF

Selected References

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

  1. Abney E. R., Cooper M. D., Kearney J. F., Lawton A. R., Parkhouse R. M. Sequential expression of immunoglobulin on developing mouse B lymphocytes: a systematic survey that suggests a model for the generation of immunoglobulin isotype diversity. J Immunol. 1978 Jun;120(6):2041–2049. [PubMed] [Google Scholar]
  2. Alt F. W., Rosenberg N., Casanova R. J., Thomas E., Baltimore D. Immunoglobulin heavy-chain expression and class switching in a murine leukaemia cell line. Nature. 1982 Mar 25;296(5855):325–331. doi: 10.1038/296325a0. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Augustin A. A., Coutinho A. Specific T helper cells that activate B cells polyclonally. In vitro enrichment and cooperative function. J Exp Med. 1980 Mar 1;151(3):587–601. doi: 10.1084/jem.151.3.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Benner R., Coutinho A., Rijnbeek A. M., van Oudenaren A., Hooijkaas H. Immunoglobulin isotype expression. II. Frequency analysis in mitogen-reactive B cells. Eur J Immunol. 1981 Oct;11(10):799–804. doi: 10.1002/eji.1830111012. [DOI] [PubMed] [Google Scholar]
  7. Coutinho A., Augustin A. A., Forni L., Fischer-Lindahl K. Genetics of a non-H-2 antigen that stimulates "unrestricted" helper T cells and MLR. J Immunol. 1981 Jul;127(1):21–25. [PubMed] [Google Scholar]
  8. Eckhardt L. A., Tilley S. A., Lang R. B., Marcu K. B., Birshtein B. K. DNA rearrangements in MPC-11 immunoglobulin heavy chain class-switch variants. Proc Natl Acad Sci U S A. 1982 May;79(9):3006–3010. doi: 10.1073/pnas.79.9.3006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Forni L., Coutinho A. The production of membrane or secretory forms immunoglobulins is regulated by C-gene-specific signals. Nature. 1982 Sep 9;299(5879):173–175. doi: 10.1038/299173a0. [DOI] [PubMed] [Google Scholar]
  10. Francus T., Dharmgrongartama B., Campbell R., Scharff M. D., Birshtein B. K. IgG2a-producing variants of an IgG2b-producing mouse myeloma cell line. J Exp Med. 1978 Jun 1;147(6):1535–1550. doi: 10.1084/jem.147.6.1535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Kataoka T., Miyata T., Honjo T. Repetitive sequences in class-switch recombination regions of immunoglobulin heavy chain genes. Cell. 1981 Feb;23(2):357–368. doi: 10.1016/0092-8674(81)90131-8. [DOI] [PubMed] [Google Scholar]
  13. Lang R. B., Stanton L. W., Marcu K. B. On immunoglobulin heavy chain gene switching: two gamma 2b genes are rearranged via switch sequences in MPC-11 cells but only one is expressed. Nucleic Acids Res. 1982 Jan 22;10(2):611–630. doi: 10.1093/nar/10.2.611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Martinez-Alonso C., Coutinho A., Augustin A. A. Immunoglobulin C-gene expression. I. The commitment to IgG subclass of secretory cells is determined by the quality of the nonspecific stimuli. Eur J Immunol. 1980 Sep;10(9):698–702. doi: 10.1002/eji.1830100908. [DOI] [PubMed] [Google Scholar]
  15. Pernis B., Forni L., Luzzati A. L. Synthesis of multiple immunoglobulin classes by single lymphocytes. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):175–183. doi: 10.1101/sqb.1977.041.01.023. [DOI] [PubMed] [Google Scholar]
  16. Radbruch A., Liesegang B., Rajewsky K. Isolation of variants of mouse myeloma X63 that express changed immunoglobulin class. Proc Natl Acad Sci U S A. 1980 May;77(5):2909–2913. doi: 10.1073/pnas.77.5.2909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Roeder W., Maki R., Traunecker A., Tonegawa S. Linkage of the four gamma subclass heavy chain genes. Proc Natl Acad Sci U S A. 1981 Jan;78(1):474–478. doi: 10.1073/pnas.78.1.474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rosenberg Y. J., Chiller J. M. Ability of antigen-specific helper cells to effect a class-restricted increase in total Ig-secreting cells in spleens after immunization with the antigen. J Exp Med. 1979 Sep 19;150(3):517–530. doi: 10.1084/jem.150.3.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Shimizu A., Takahashi N., Yamawaki-Kataoka Y., Nishida Y., Kataoka T., Honjo T. Ordering of mouse immunoglobulin heavy chain genes by molecular cloning. Nature. 1981 Jan 15;289(5794):149–153. doi: 10.1038/289149a0. [DOI] [PubMed] [Google Scholar]
  20. Slack J., Der-Balian G. P., Nahm M., Davie J. M. Subclass restriction of murine antibodies. II. The IgG plaque-forming cell response to thymus-independent type 1 and type 2 antigens in normal mice and mice expressing an X-linked immunodeficiency. J Exp Med. 1980 Apr 1;151(4):853–862. doi: 10.1084/jem.151.4.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wabl M. R., Forni L., Loor F. Switch in immunoglobulin class production observed in single clones of committed lymphocytes. Science. 1978 Mar 10;199(4333):1078–1080. doi: 10.1126/science.305113. [DOI] [PubMed] [Google Scholar]
  22. Yaoita Y., Kumagai Y., Okumura K., Honjo T. Expression of lymphocyte surface IgE does not require switch recombination. Nature. 1982 Jun 24;297(5868):697–699. doi: 10.1038/297697a0. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES