Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1987 Aug 1;166(2):391–403. doi: 10.1084/jem.166.2.391

Regulated progression of B lymphocyte differentiation from cultured fetal liver

PMCID: PMC2189598  PMID: 3496415

Abstract

Lymphoid fetal liver cultures (LFLC) are long-term, nontransformed cultures of early B lymphoid lineage cells which appear developmentally blocked at the pre-B stage in vitro. When injected into severe combined immunodeficient (SCID) mice, cells from LFLC could reconstitute splenic B lymphocytes and serum IgM. T lymphocyte reconstitution was not observed and serum IgG levels were very low. IgG3 was the predominant gamma subisotype in the serum of the LFLC-reconstituted mice, indicating impaired class switching in these B lymphocytes. When thymocytes were coinjected with LFLC, the B lymphocytes were able to class switch fully and respond to T-dependent antigens. These serological responses were heterogeneous. This experimental system allows separation of three B lymphocyte developmental stages: early differentiation in vitro, progression to IgM secretion in vivo, and late differentiation dependent upon mature T lymphocytes in vivo. The unique advantage of this system is the ability to regulate the B lymphocyte developmental pathway in a defined, stepwise manner.

Full Text

The Full Text of this article is available as a PDF (1.3 MB).

Selected References

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

  1. Bosma G. C., Custer R. P., Bosma M. J. A severe combined immunodeficiency mutation in the mouse. Nature. 1983 Feb 10;301(5900):527–530. doi: 10.1038/301527a0. [DOI] [PubMed] [Google Scholar]
  2. Denis K. A., Treiman L. J., St Claire J. I., Witte O. N. Long-term cultures of murine fetal liver retain very early B lymphoid phenotype. J Exp Med. 1984 Oct 1;160(4):1087–1101. doi: 10.1084/jem.160.4.1087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Denis K. A., Witte O. N. Long-term culture systems for analysis of early B lymphocyte development. Int Rev Immunol. 1987 Mar;2(3):285–305. doi: 10.3109/08830188709044758. [DOI] [PubMed] [Google Scholar]
  4. Dorshkind K., Denis K. A., Witte O. N. Lymphoid bone marrow cultures can reconstitute heterogeneous B and T cell-dependent responses in severe combined immunodeficient mice. J Immunol. 1986 Dec 1;137(11):3457–3463. [PubMed] [Google Scholar]
  5. Dorshkind K., Keller G. M., Phillips R. A., Miller R. G., Bosma G. C., O'Toole M., Bosma M. J. Functional status of cells from lymphoid and myeloid tissues in mice with severe combined immunodeficiency disease. J Immunol. 1984 Apr;132(4):1804–1808. [PubMed] [Google Scholar]
  6. Honjo T. Immunoglobulin genes. Annu Rev Immunol. 1983;1:499–528. doi: 10.1146/annurev.iy.01.040183.002435. [DOI] [PubMed] [Google Scholar]
  7. Keller G., Paige C., Gilboa E., Wagner E. F. Expression of a foreign gene in myeloid and lymphoid cells derived from multipotent haematopoietic precursors. Nature. 1985 Nov 14;318(6042):149–154. doi: 10.1038/318149a0. [DOI] [PubMed] [Google Scholar]
  8. Kincade P. W. Formation of B lymphocytes in fetal and adult life. Adv Immunol. 1981;31:177–245. doi: 10.1016/s0065-2776(08)60921-9. [DOI] [PubMed] [Google Scholar]
  9. Kincade P. W., Paige C. J., Parkhouse R. M., Lee G. Characterization of murine colony-forming B cells. I. Distribution, resistance to anti-immunoglobulin antibodies, and expression of Ia antigens. J Immunol. 1978 Apr;120(4):1289–1294. [PubMed] [Google Scholar]
  10. Melchers F., Von Boehmer H., Phillips R. A. B-lymphocyte subpopulations in the mouse. Organ distribution and ontogeny of immunoglobulin-synthesizing and of mitogen-sensitive cells. Transplant Rev. 1975;25:26–58. doi: 10.1111/j.1600-065x.1975.tb00725.x. [DOI] [PubMed] [Google Scholar]
  11. Mongini P. K., Paul W. E., Metcalf E. S. T cell regulation of immunoglobulin class expression in the antibody response to trinitrophenyl-ficoll. Evidence for T cell enhancement of the immunoglobulin class switch. J Exp Med. 1982 Mar 1;155(3):884–902. doi: 10.1084/jem.155.3.884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mongini P. K., Stein K. E., Paul W. E. T cell regulation of IgG subclass antibody production in response to T-independent antigens. J Exp Med. 1981 Jan 1;153(1):1–12. doi: 10.1084/jem.153.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mosier D. E., Zitron I. M., Mond J. J., Ahmed A., Scher I., Paul W. E. Surface immunoglobulin D as a functional receptor for a subclass of B lymphocytes. Immunol Rev. 1977;37:89–104. doi: 10.1111/j.1600-065x.1977.tb00246.x. [DOI] [PubMed] [Google Scholar]
  14. Nottenburg C., Weissman I. L. Cmu gene rearrangement of mouse immunoglobulin genes in normal B cells occurs on both the expressed and nonexpressed chromosomes. Proc Natl Acad Sci U S A. 1981 Jan;78(1):484–488. doi: 10.1073/pnas.78.1.484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
  16. Paige C. J., Kincade P. W., Moore M. A., Lee G. The fate of fetal and adult B-cell progenitors grafted into immunodeficient CBA/N mice. J Exp Med. 1979 Sep 19;150(3):548–563. doi: 10.1084/jem.150.3.548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Schuler W., Weiler I. J., Schuler A., Phillips R. A., Rosenberg N., Mak T. W., Kearney J. F., Perry R. P., Bosma M. J. Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency. Cell. 1986 Sep 26;46(7):963–972. doi: 10.1016/0092-8674(86)90695-1. [DOI] [PubMed] [Google Scholar]
  18. Taylor R. B., Wortis H. H. Thymus dependence of antibody response: variation with dose of antigen and class of antibody. Nature. 1968 Nov 30;220(5170):927–928. doi: 10.1038/220927a0. [DOI] [PubMed] [Google Scholar]
  19. Vitetta E. S., Brooks K., Chen Y. W., Isakson P., Jones S., Layton J., Mishra G. C., Pure E., Weiss E., Word C. T-cell-derived lymphokines that induce IgM and IgG secretion in activated murine B cells. Immunol Rev. 1984 Apr;78:137–157. doi: 10.1111/j.1600-065x.1984.tb00480.x. [DOI] [PubMed] [Google Scholar]
  20. Wall R., Kuehl M. Biosynthesis and regulation of immunoglobulins. Annu Rev Immunol. 1983;1:393–422. doi: 10.1146/annurev.iy.01.040183.002141. [DOI] [PubMed] [Google Scholar]
  21. Whitlock C. A., Robertson D., Witte O. N. Murine B cell lymphopoiesis in long term culture. J Immunol Methods. 1984 Mar 16;67(2):353–369. doi: 10.1016/0022-1759(84)90475-7. [DOI] [PubMed] [Google Scholar]
  22. Whitlock C. A., Ziegler S. F., Treiman L. J., Stafford J. I., Witte O. N. Differentiation of cloned populations of immature B cells after transformation with Abelson murine leukemia virus. Cell. 1983 Mar;32(3):903–911. doi: 10.1016/0092-8674(83)90075-2. [DOI] [PubMed] [Google Scholar]
  23. Whitlock C., Denis K., Robertson D., Witte O. In vitro analysis of murine B-cell development. Annu Rev Immunol. 1985;3:213–235. doi: 10.1146/annurev.iy.03.040185.001241. [DOI] [PubMed] [Google Scholar]
  24. Yancopoulos G. D., Alt F. W. Regulation of the assembly and expression of variable-region genes. Annu Rev Immunol. 1986;4:339–368. doi: 10.1146/annurev.iy.04.040186.002011. [DOI] [PubMed] [Google Scholar]

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

RESOURCES