Differentiation in the I.29 B Cell Lymphoma: Precommitment to IgA or IgE Switch in Individual IgM+ Clones

  • R. Sitia
  • C. Alberini
  • R. Biassoni
  • S. DeAmbrosis
  • D. Vismara
Part of the NATO ASI Series book series (NSSA, volume 123)

Abstract

Blymphocytes undergo during their development several sequential rearrangements at the immunoglobulin (Ig) loci (1). The first event is a D-JH recombination that usually takes place at both the heavy chain (IgH) loci, and is then followed by rearrangement of one of the numerous VHgenes to the DJHcomplex (2). When a functional VDJ rearrangement has taken place, synthesis of μ Polypeptide ensues and rearragments of the light chain loci begin. A K-λ hyerarchy has been demonstrated in both human and mouse B cells (3,4). A successful heavy chain gene recombination stops any further rearrangement at the IgH locus (5,6), and possibly stimulates IgL recombination. Similarly the creation of a productive light chain gene blocks further recombinations at the IgL loci (5). Subsequently IgM molecules are synthetized and expressed on the cell surface by lymphocytes (7). The latter may coexpress IgD through alternative splicing of the VDJ - Cμ -C δ transcription unit (8). IgM+ B cell may undergo a second recombinatorial event at the IgH locus, termed isotype switching. This event generally implies the deletion of Cμ, Cδ and all the CHgenes which are located 5′ to the one CH gene that will be expressed (9,10). Although the sequences mediating switch recombination have been isolated and determined (9–11), rather little is known about the mechanisms regulating isotype switching. The question of how an IgM+B lymphocyte decides which CH gene to recombine is still open. It is well known that certain antigens or routes of immunization result in vivo in the predominance of a given isotype (12). On the other hand several in vitro experiments have shown that more than one isotype can be produced by the progeny of a single B cell (13–15). Isotype switching is not the only differentiative option of an IgM+ B cell. The latter may infact respond to antigen or mitogen by differentiating into IgM secreting plasmacells (7). It is generally accepted that plasmacell may undergo a very limited number of divisions.

Keywords

Phenol Lymphoma Recombination Agarose Bromide 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1).
    Tonegawa S. (1983). Nature 302: 575.CrossRefGoogle Scholar
  2. 2).
    Alt F.W. et al. (1981). Cell 27:381.MathSciNetCrossRefGoogle Scholar
  3. 3).
    Korsmeyer S. et al. (1981). Proc. Natl. Acad. Sci. USA.Google Scholar
  4. 4).
    Alt. F.W. et al. (1984) EMBO J. 3: 1209.Google Scholar
  5. 5).
    Rusconi S. and G. Kohler (1985) Nature 314: 330.CrossRefGoogle Scholar
  6. 6).
    Ritchie K.A., R.L. Brinster and U. Storb (1984). Nature 312:517.CrossRefGoogle Scholar
  7. 7).
    Calvert J. A. et al (198) Semin. Hematol.Google Scholar
  8. 8).
    Knapp M.R. et al. (1982) Proc. Natl. Acad. Sci. USA 79: 2996.CrossRefGoogle Scholar
  9. 9).
    Sakano H. et al. (1980). Nature.Google Scholar
  10. 10).
    Davis M.M, S.K. and L.E. Hood (1980). Science 209: 1CrossRefGoogle Scholar
  11. 11).
    Kataoka T., T. Mijata and T. Honjo (1981). Cell 23: 357.CrossRefGoogle Scholar
  12. 12).
    Katz D.H. (1980) Immunology.Google Scholar
  13. 13).
    Gearhart P.3., N.H. Sigal and N.R. Klinman (1975). Proc. Natl. Acad. Sci. 72:1707.CrossRefGoogle Scholar
  14. 14).
    Mongini P., W.E. Paul and E.S. Metcalf (1983) J.Exp. Med. 157:69.CrossRefGoogle Scholar
  15. 15).
    Teale 3.L. (1983) J. Immunol. 131: 2170.Google Scholar
  16. 16).
    Sitia R., A. Rubartelli and U. Hämmerling (1981). J.Immunol 127:1388.Google Scholar
  17. 17).
    Stavnezer J. et al. (1982) Mol. Cell. Biol. 2:1002.Google Scholar
  18. 18).
    Stavnezer J., S. Sirlin and J. Abbott (1985) J. Exp. Med. 161:577.CrossRefGoogle Scholar
  19. 19).
    Sitia R. et al. (1985) Eur. J. Immunol. 15:570.CrossRefGoogle Scholar
  20. 20).
    Sitia R. et al. (1985) J. Immunol. 135: 2859.Google Scholar
  21. 21).
    Marcu K.B. et al (1980) Cell 22:187.MathSciNetCrossRefGoogle Scholar
  22. 22).
    Nishida Y. et al. (1981) Proc. Natl. Acad. Sci. USA. 78:1581.CrossRefGoogle Scholar
  23. 23).
    Rogers J., P. Clarke and R.W. Salser (1979). Nucleic Acid Res. 6:3305.CrossRefGoogle Scholar
  24. 24).
    Tilley S.A. and B. Birhstein (1985). J. Exp. Med. 162:675.CrossRefGoogle Scholar
  25. 25).
    Moller J. Ed. (1984) Immunol. Rev. Vol 78.Google Scholar
  26. 26).
    Layton J.E. et al. (1984) J.Exp. Med. 160: 1850.CrossRefGoogle Scholar
  27. 27).
    Sitia R. (1985). Mol. Immunol. 22:1289.CrossRefGoogle Scholar
  28. 28).
    Weintraub H., A. Larsen and G. Groudine (1981) Cell 24:333.CrossRefGoogle Scholar
  29. 29).
    Yancopoulos G.D. and F.W. Alt (1985). Cell. 40: 271.CrossRefGoogle Scholar
  30. 30).
    Stavnezer J. J. Abbott and Sirlin (1984) Curr. Top. Microbiol. Immunol. 113:109.Google Scholar
  31. 31).
    Stavnezer J. and S. Sirlin (1986) EMBO J. (in press).Google Scholar
  32. 32).
    Yaoita Y. et al. (1982) Nature 297:697.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • R. Sitia
    • 1
  • C. Alberini
    • 1
  • R. Biassoni
    • 1
  • S. DeAmbrosis
    • 1
  • D. Vismara
    • 1
  1. 1.Laboratory of Molecular BiologyIstituto Nazionale per la Ricerca sul CancroGenovaItalia

Personalised recommendations