Growth Requirements of B Lineage Lymphocytes From Scid and Normal Mice

  • G. Lee
  • K. Medina
  • P. W. Kincade
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 152)


Long term culture techniques provide unique approaches to dissecting components of the bone marrow microenvironment. These procedures are particularly effective for studies utilizing mice, where it is possible to selectively propagate either myeloid, or B lineage lymphoid cells for many months (Whitlock et al. 1984). Several laboratories have established and cloned “stromal” cell lines which support myelopoiesis and/or lymphopoiesis, as well as lymphocyte clones which depend on them for growth. Progress is also being made in learning which regulatory cytokines are made in these circumstances, and conditions favoring their production. However, there are indications that these model systems do not fully reflect the cellular and molecular heterogeneity that exists in vivo (Kincade et al. 1988). This has become particularly noteworthy from culture studies of genetically determined abnormalities, including SCID. Further comparison of the behavior of such defective cells in vivo and in vitro should be informative about mechanisms involved in normal lymphopoiesis.


Stromal Cell Bone Marrow Stromal Cell Severe Combine Immunodeficiency Bone Marrow Microenvironment 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. Allen TD, Dexter TM (1984) The essential cells of the hemopoietic microenvironment. Exp Hematol 12:517–521PubMedGoogle Scholar
  2. Bosma GC, Fried M, Custer RP, Carroll A, Gibson DM, Bosma MJ (1988) Evidence of functional lymphocytes in some (Leaky) scid mice. J Exp Med 167:1016–1033PubMedCrossRefGoogle Scholar
  3. Collins LS, Dorshkind K (1987) A stromal cell line from myeloid long-term bone marrow cultures can support myelopoiesis and B lymphopoiesis. J Immunol 138:1082–1087PubMedGoogle Scholar
  4. Dorshkind K, Pollock SB, Bosma MJ, Phillips RA (1985) Natural killer (NK) cells are present in mice with severe combined immunodeficiency (SCID). J Immunol 134:37–89Google Scholar
  5. Hayashi S-I, Witte PL, Kincade PW (1989) The Xid mutation affects hemopoiesis in long term cultures of murine bone marrow. J Immunol 142:444–451PubMedGoogle Scholar
  6. Hirayoshi K, Nishikawa S, Kina T, Hatanaka M, Habu S, Nomura T, Katsura Y (1987) Immunoglobulin heavy chain gene diversification in the long-term bone marrow culture of normal mice and mice with severe combined immunodeficiency. Eur J Immunol 17:1051–1057PubMedCrossRefGoogle Scholar
  7. Hunt P, Robertson D, Weiss D, Rennick D, Lee F, Witte ON (1987) A single bone marrow-derived stromal cell type supports the in vitro growth of early lymphoid and myeloid cells. Cell 48:997–1007PubMedCrossRefGoogle Scholar
  8. Kierney PC, Dorshkind K (1987) B lymphocyte precursors and myeloid progenitors survive in diffusion chamber cultures but B cell differentiation requires close association with stromal cells. Blood 70:1418–1424PubMedGoogle Scholar
  9. Kincade PW (1987) Experimental models for understanding B lymphocyte formation. Adv Immunol 41:181–267PubMedCrossRefGoogle Scholar
  10. Kincade PW, Lee G, Pietrangeli CE, Hayashi S-I, Gimble, JM (1988) Cells and molecules that regulate B lymphopoiesis in bone marrow. Ann Rev Immunol 7:111–143CrossRefGoogle Scholar
  11. King AG, Wierda D, Landreth KS (1988) Bone marrow stromal cell regulation of Blymphopoiesis: 1. The role of macrophages, interleukin-1, and interleukin-4 in pre-B cell maturation. J Immunol 141:2016–2026PubMedGoogle Scholar
  12. Landreth KS, Dorshkind K (1988) Pre-B cell generation potentiated by soluble factors from a bone marrow stromal cell line. J Immunol 140:845–852PubMedGoogle Scholar
  13. Lee G, Ellingsworth LR, Gillis S, Wall R, Kincade PW (1987) B transforming growth factors are potential regulators of B lymphopoiesis. J Exp Med 166:1290–1299PubMedCrossRefGoogle Scholar
  14. Lee G, Namen AE, Gillis S, Ellingsworth LR, Kincade PW (1989) Normal B cell Precursors responsive to recombinant murine interleukin 7 (IL-7) and inhibition of IL-7 activity by TGF-ß. J Immunol (in press)Google Scholar
  15. Lemoine FM, Humphries RK, Abraham SDM, Krystal G, Eaves CJ (1988) Partial Characterization of a Novel Stromal Cell-derived Pre-B-cell Growth Factor Active on Normal and Immortialized Pre-B Cells. Exp Hematol 16:718–726PubMedGoogle Scholar
  16. Namen AE, Lupton S, Hjerrild K, Wignall J, Mochizuki DY, Schmierer A, Mosley B, March CJ, Urdal D, Gillis S, Cosman D, Goodwin RG (1988) Stimulation of B-cell progenitors by cloned murine interleukin-7. Nature 333:571–573PubMedCrossRefGoogle Scholar
  17. Pietrangeli CE, Hayashi S-I, Kincade PW (1988) Stromal cell lines which support lymphocyte growth: Characterization, sensitivity to radiation and responsiveness to growth factors. Eur J Immunol 18:863–872PubMedCrossRefGoogle Scholar
  18. Rennick D, Yang G, Gemmell L, Lee F (1987) Control of hemopoiesis by a bone marrow stromal cell clone: Lipopolysaccharide-and interleukin-1-inducible production of colony-stimulating factors. Blood 69:682–691PubMedGoogle Scholar
  19. Whitlock CA, Robertson D, Witte ON (1984) Murine B cell lymphopoiesis in long-term culture. J Immunol Methods 67:353–369PubMedCrossRefGoogle Scholar
  20. Whitlock CA, Tidmarsh GF, Muller-Sieburg C, Weissman IL (1987) Bone marrow stromal cell lines with lymphopoietic activity express high levels of a pre-B neoplasia-associated molecule. Cell 48:1009–10021PubMedCrossRefGoogle Scholar
  21. Witte PL, Burrows PD, Kincade PW, Cooper MD (1987a) Characterization of B lymphocyte lineage progenitor cells from mice with severe combined immune deficiency disease (SCID) made possible by long term culture. J Immunol 138:2698–2705Google Scholar
  22. Witte PL, Robinson M, Henley A, Low MG, Stiers DL, Perkins S, Fleischman RA, Kincade PW (1987b) Relationships between B-lineage lymphocytes and stromal cells in long term bone marrow cultures. Eur J Immunol 17:1473–1484CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1989

Authors and Affiliations

  • G. Lee
    • 1
  • K. Medina
    • 1
  • P. W. Kincade
    • 1
  1. 1.Oklahoma Medical Research FoundationOklahoma CityUSA

Personalised recommendations