B Cell Development in Fetal Liver

  • Fritz Melchers
  • Andreas Strasser
  • Steven R. Bauer
  • Akira Kudo
  • Philipp Thalmann
  • Antonius Rolink
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 292)


Embryonic development of B lymphocytes in the mouse is remarkably well programmed in time of gestation. A first wave of development in embryonic blood and placenta1,2 reaches its peak of mitogen-reactive precursors at day 12 of gestation. This is followed by a second wave in fetal liver, which reaches its peak of mitogen-reactive B cells around birth, i.e., at day 19 of gestation.3,4 This development also occurs when embryonic bodies with blood islands and beating heart cells develop in vitro from embryonic stem cells (U. Chen and F. Melchers, manuscript in preparation). Since mitogen-reactive precursors develop from embryonic stem cells with much the same time schedule in vitro as they do in vivo cell cycle times, numbers of divisions and differentiation steps along the embryonic B lymphocyte development must be tightly controlled. We have investigated B cell development in fetal liver of the mouse on the cellular and molecular level in order to understand how such ordered development in time of gestation is achieved.


Cell Development Fetal Liver Hemopoietic Stem Cell Cell Cycle Time Stromal Cell Line 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    F. Melchers, Murine embryonic B lymphocyte development in the placenta, Nature 277:219 (1979).PubMedCrossRefGoogle Scholar
  2. 2.
    F. Melchers and J. Abramczuk, Murine embryonic blood between day 10 and 13 of gestation as a source of immature precursor B cells, Eur. J. Immunol. 10:763 (1980).PubMedCrossRefGoogle Scholar
  3. 3.
    F. Melchers, B lymphocyte development in fetal liver. I. Development of reactivities to B cell mitogens in vivo and in vitro, Eur. J. Immunol. 7:476 (1977).PubMedCrossRefGoogle Scholar
  4. 4.
    F. Melchers, B lymphocyte development in fetal liver. II. Frequencies of precursor B cells during gestation, Eur. J. Immunol7:482 (1977).PubMedCrossRefGoogle Scholar
  5. 5.
    E. Gronowicz, A. Coutinho, and F. Melchers, A plaque assay for all cells secreting Ig of a given type or class, Eur. J. Immunol. 6:588 (1976).PubMedCrossRefGoogle Scholar
  6. 6.
    J. Andersson, A. Coutinho, W. Lernhardt, and F. Melchers, Clonal growth and maturation to immunoglobulin secretion in vitro of every growth-inducible B lymphocyte, Cell 11:27 (1977).CrossRefGoogle Scholar
  7. 7.
    C. N. Berger, In situ hybridization of immunoglobulin-specific RNA in single cells of the B lymphocyte lineage with radio-labelled DNA probes, EMBO J. 5:85 (1986).PubMedGoogle Scholar
  8. 8.
    N. Sakaguchi and F. Melchers, 5, a new light-chain-related locus selectively expressed in pre-B lymphoyctes, Nature 324:579 (1986).PubMedCrossRefGoogle Scholar
  9. 9.
    A. Kudo, N. Sakaguchi, and F. Melchers, Organization of the murine Ig-related 5 gene transcribed selectively in pre-B lymphocytes, EMBO J. 6:103 (1987).PubMedGoogle Scholar
  10. 10.
    A. Kudo and F. Melchers, A second gene, V reB in the 15 locus of the mouse, which appears to be selectively expressed in pre-B lymphocytes, EMBO J. 6:2267 (1987).PubMedGoogle Scholar
  11. 11.
    A. Strasser, PB76: a novel surface glycoprotein preferentially expressed on mouse pre-B cells and plasma cells detected by the monoclonal antibody G-5–2,Eur. J. Immunol. 18:1803 (1988).PubMedCrossRefGoogle Scholar
  12. 12.
    C. Marquez, A. de la Hera, E. Leonardo, L. Pezzi, A. Strasser, and A. C. Martinez, Identity of PB76 differentiation antigen and lymphocyte alkaline phosphatase, Eur. J. Immunol. 20:947 (1990).PubMedCrossRefGoogle Scholar
  13. 13.
    F. Melchers, A. Strasser, S. R. Bauer, A. Kudo, P. Thalmann, and A. Rolink, Cellular stages and molecular steps of murine B cell development, Cold Spring Harb. Symp. Quant. Biol. 54:183 (1990).CrossRefGoogle Scholar
  14. 14.
    A. Strasser, T. Rolink, and F. Melchers, One synchronous wave of B cell development in mouse fetal liver changes at day 16 of gestation from dependence to independence of a stromal cell environment, J. Exp. Med. 170:1973 (1989).PubMedCrossRefGoogle Scholar
  15. 15.
    S. Tonegawa, Somatic generation of antibody diversity, Nature 302:575 (1983).PubMedCrossRefGoogle Scholar
  16. 16.
    P. W. Kincade, Experimental models for understanding B lymphocyte formation, Adv. Immunol. 41:181 (1987).PubMedCrossRefGoogle Scholar
  17. 17.
    P. W. Kincade, G. Lee, C. W. Paige, and M. P. Scheid, Cellular interactions affecting the maturation of murine B lymphocyte precursors in vitro, J. Immunol. 127:255 (1981).PubMedGoogle Scholar
  18. 18.
    J. W. Coleman, J. H. K. Yeung, M. D. Tingle, and B. K. Park, Enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to protein-reactive drugs and metabolites: criteria for identification of antibody activity, J. Immunol. Meth. 88:37 (1986).CrossRefGoogle Scholar
  19. 19.
    C. Whitlock, K. Denis, D. Robertson, and O. N. Witte, In vitro analysis of murine B-cell development, Ann. Rev. Immunol. 3:213 (1985).CrossRefGoogle Scholar
  20. 20.
    G. H. Gisler, A. Söderberg, and M. Kamber, Functional maturation of murine B lymphocyte precursors. II. Analysis of cells required from the bone marrow micro-environment, J. Immunol 138:2433 (1987).PubMedGoogle Scholar
  21. 21.
    P. L. Witte, M. Robertson, A. Henley, M. G. Low, D. L. Stiers, S. Perkins, R. A. Fleischman, and P. W. Kincade, Relationship between B-lineage lymphocytes and stromal cells in long-term bone marrow cultures, Eur. J. Immunol. 17:1473 (1987).PubMedCrossRefGoogle Scholar
  22. 22.
    T. Kinashi, K. Inaba, T. Tsubata, K. Tashiro, R. Palacios, and T. Honjo, Differentiation of an interleukin 3-dependent precursor B cell clone into immunoglobulin-producing cells in vitro, Proc. Natl. Acad. Sci. U. S. A. 85:4473 (1988).PubMedCrossRefGoogle Scholar
  23. 23.
    L. E. Pietrangeli, S.-I. Hayashi, and P. W. Kincade, Stromal cell lines which support lymphocyte growth: characterization, sensitivity to radiation and responsiveness to growth factors, Eur. J. Immunol. 18:863 (1988).Google Scholar
  24. 24.
    R. Palacios, S. Stuber, and A. Rolink, Epigenetic influences of bone marrow stroma and liver stroma on the developmental potential of LY1 plus pro-B lymphocytes, Eur. J. Immunol 19:347 (1989).PubMedCrossRefGoogle Scholar
  25. 25.
    S. I. Nishikawa, M. Ogawa, S. Nishikawa, T. Kunnisada, and H. Kodama, B lymphopoiesis on stromal cell clone: stromal cell clones acting on different stages of B cell differentiation, Eur. J. Immunol. 18:1767 (1988).PubMedCrossRefGoogle Scholar
  26. 26.
    M. Ogawa, S. Nishikawa, Y. Ikuta, F. Yamamura, M. Naito, K. Takahashi, and S. I. Nishikawa, B cell ontogeny in murine embryo studied by a culture system with the monolayer of a stroma cell clone, ST2: B cell progenitor develops first in the embryonal body rather than in the yolk sac, EM BO J. 7:1337 (1988).Google Scholar
  27. 27.
    H. A. Kodama, Y. Amagai, H. Koyama, and S. Kasai, A new preadipose cell line derived from newborn mouse calvaria can promote the proliferation of pluripotent hemopoietic stem cells in vitro, J. Cell. Physiol. 112:89 (1982).PubMedCrossRefGoogle Scholar
  28. 28.
    H. A. Kodama, H. Sudo, H. Koyama, S. Kasai, and S. Yamamoto, In vitro hemopoiesis within a microenvironment created by MC3T3-G2/PA6 preadipocytes, J. Cell. Physiol. 118:233 (1984).PubMedCrossRefGoogle Scholar
  29. 29.
    H. A. Kodama, H. Hagiwara, H. Sudo, Y. Amagai, T. Yokota, N. Arai, and Y. Kitamura, MC3T3-G2/PA6 preadipocytes support in vitro proliferation of hemopoietic stem cells through a mechanism different from that of interleukin 3, J. Cell. Biol. 129:20 (1986).Google Scholar
  30. 30.
    T. Sudo, M. Ito, Y. Ogawa, M. Lizuka, A. Kodama, T. Kumisada, S.-I. Hayashi, M. Ogawa, K. Sakai, S. Nishikawa, and S. I. Nishikawa, Interleukin 7 production and function in stromal cell-dependent B cell development, J. Exp. Med. 170:338 (1989).CrossRefGoogle Scholar
  31. 31.
    A. E. Namen, S. Lupton, K. Kjerrild, J. Urignall, D. Y. Mochizuki, A. Schmierer, B. Mosley, C. J. March, D. Urdai, S. Gillis, D. Cosman, and R. G. Goodwin, Stimulation of B-cell progenitors by cloned murine interleukin-7, Nature 333:571 (1988).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Fritz Melchers
    • 1
  • Andreas Strasser
    • 1
  • Steven R. Bauer
    • 1
  • Akira Kudo
    • 1
  • Philipp Thalmann
    • 1
  • Antonius Rolink
    • 1
  1. 1.Basel Institute for ImmunologyBaselSwitzerland

Personalised recommendations