Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1988 Jul 1;168(1):389–407. doi: 10.1084/jem.168.1.389

Relationships between B cell and myeloid differentiation. Studies with a B lymphocyte progenitor line, HAFTL-1

PMCID: PMC2188967  PMID: 3294335

Abstract

A cell line, HAFTL-1, derived by in vitro transformation of fetal liver cells with v-Ha-ras, was found to have molecular and phenotypic characteristics of pro-B cells recently committed to the Ly-1+ B cell differentiation pathway. Stimulation of these cells with LPS resulted in their differentiation within either the B or myelomonocytic lineages. Thus, lines derived from LPS-stimulated HAFTL-1 cells were shown to be clonally related, as evidenced by common v-ras integrations, but to exhibit characteristics of pre-B cells (ThB expression, continuing DJ heavy chain rearrangements) or mature macrophages (expression of Mac-1 and Mac-2, lysozyme and nonspecific esterase production, phagocytosis) while maintaining their Ly-1+ phenotype. These results suggest that events resulting in the irrevocable commitment to a single lineage occur late in differentiation, at least within the pathway yielding Ly-1+ B cells and a proposed subpopulation of Ly-1+ monocytes and macrophages. Final commitment to these lineages is carefully orchestrated, as evidenced by restricted expression of Ly-5 isoforms and production of IgH transcripts.

Full Text

The Full Text of this article is available as a PDF (1.6 MB).

Selected References

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

  1. Alessandrini A., Pierce J. H., Baltimore D., Desiderio S. V. Continuing rearrangement of immunoglobulin and T-cell receptor genes in a Ha-ras-transformed lymphoid progenitor cell line. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1799–1803. doi: 10.1073/pnas.84.7.1799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alt F. W., Yancopoulos G. D., Blackwell T. K., Wood C., Thomas E., Boss M., Coffman R., Rosenberg N., Tonegawa S., Baltimore D. Ordered rearrangement of immunoglobulin heavy chain variable region segments. EMBO J. 1984 Jun;3(6):1209–1219. doi: 10.1002/j.1460-2075.1984.tb01955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Alt F., Rosenberg N., Lewis S., Thomas E., Baltimore D. Organization and reorganization of immunoglobulin genes in A-MULV-transformed cells: rearrangement of heavy but not light chain genes. Cell. 1981 Dec;27(2 Pt 1):381–390. doi: 10.1016/0092-8674(81)90421-9. [DOI] [PubMed] [Google Scholar]
  4. Basch R. S., Berman J. W. Thy-1 determinants are present on many murine hematopoietic cells other than T cells. Eur J Immunol. 1982 May;12(5):359–364. doi: 10.1002/eji.1830120502. [DOI] [PubMed] [Google Scholar]
  5. Bauer S. R., Holmes K. L., Morse H. C., 3rd, Potter M. Clonal relationship of the lymphoblastic cell line P388 to the macrophage cell line P388D1 as evidenced by immunoglobulin gene rearrangements and expression of cell surface antigens. J Immunol. 1986 Jun 15;136(12):4695–4699. [PubMed] [Google Scholar]
  6. Boyd A. W., Schrader J. W. Derivation of macrophage-like lines from the pre-B lymphoma ABLS 8.1 using 5-azacytidine. Nature. 1982 Jun 24;297(5868):691–693. doi: 10.1038/297691a0. [DOI] [PubMed] [Google Scholar]
  7. Burrows P., LeJeune M., Kearney J. F. Evidence that murine pre-B cells synthesise mu heavy chains but no light chains. Nature. 1979 Aug 30;280(5725):838–840. doi: 10.1038/280838a0. [DOI] [PubMed] [Google Scholar]
  8. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  9. Coffman R. L. Surface antigen expression and immunoglobulin gene rearrangement during mouse pre-B cell development. Immunol Rev. 1982;69:5–23. doi: 10.1111/j.1600-065x.1983.tb00446.x. [DOI] [PubMed] [Google Scholar]
  10. Coleclough C., Perry R. P., Karjalainen K., Weigert M. Aberrant rearrangements contribute significantly to the allelic exclusion of immunoglobulin gene expression. Nature. 1981 Apr 2;290(5805):372–378. doi: 10.1038/290372a0. [DOI] [PubMed] [Google Scholar]
  11. Crawford R. M., Finbloom D. S., Ohara J., Paul W. E., Meltzer M. S. B cell stimulatory factor-1 (interleukin 4) activates macrophages for increased tumoricidal activity and expression of Ia antigens. J Immunol. 1987 Jul 1;139(1):135–141. [PubMed] [Google Scholar]
  12. Dasch J. R., Jones P. P. Independent regulation of IgM, IgD, and Ia antigen expression in cultured immature B lymphocytes. J Exp Med. 1986 Apr 1;163(4):938–951. doi: 10.1084/jem.163.4.938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Davidson W. F., Fredrickson T. N., Rudikoff E. K., Coffman R. L., Hartley J. W., Morse H. C., 3rd A unique series of lymphomas related to the Ly-1+ lineage of B lymphocyte differentiation. J Immunol. 1984 Aug;133(2):744–753. [PubMed] [Google Scholar]
  14. Early P., Huang H., Davis M., Calame K., Hood L. An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH. Cell. 1980 Apr;19(4):981–992. doi: 10.1016/0092-8674(80)90089-6. [DOI] [PubMed] [Google Scholar]
  15. Ellis R. W., DeFeo D., Maryak J. M., Young H. A., Shih T. Y., Chang E. H., Lowy D. R., Scolnick E. M. Dual evolutionary origin for the rat genetic sequences of Harvey murine sarcoma virus. J Virol. 1980 Nov;36(2):408–420. doi: 10.1128/jvi.36.2.408-420.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Freeman G. J., Clayberger C., DeKruyff R., Rosenblum D. S., Cantor H. Sequential expression of new gene programs in inducer T-cell clones. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4094–4098. doi: 10.1073/pnas.80.13.4094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hayakawa K., Hardy R. R., Herzenberg L. A., Herzenberg L. A. Progenitors for Ly-1 B cells are distinct from progenitors for other B cells. J Exp Med. 1985 Jun 1;161(6):1554–1568. doi: 10.1084/jem.161.6.1554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hayakawa K., Hardy R. R., Herzenberg L. A. Peritoneal Ly-1 B cells: genetic control, autoantibody production, increased lambda light chain expression. Eur J Immunol. 1986 Apr;16(4):450–456. doi: 10.1002/eji.1830160423. [DOI] [PubMed] [Google Scholar]
  19. Holmes K. L., Langdon W. Y., Fredrickson T. N., Coffman R. L., Hoffman P. M., Hartley J. W., Morse H. C., 3rd Analysis of neoplasms induced by Cas-Br-M MuLV tumor extracts. J Immunol. 1986 Jul 15;137(2):679–688. [PubMed] [Google Scholar]
  20. Holmes K. L., Palfree R. G., Hammerling U., Morse H. C., 3rd Alleles of the Ly-17 alloantigen define polymorphisms of the murine IgG Fc receptor. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7706–7710. doi: 10.1073/pnas.82.22.7706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Holmes K. L., Pierce J. H., Davidson W. F., Morse H. C., 3rd Murine hematopoietic cells with pre-B or pre-B/myeloid characteristics are generated by in vitro transformation with retroviruses containing fes, ras, abl, and src oncogenes. J Exp Med. 1986 Aug 1;164(2):443–457. doi: 10.1084/jem.164.2.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Huang H. J., Jones N. H., Strominger J. L., Herzenberg L. A. Molecular cloning of Ly-1, a membrane glycoprotein of mouse T lymphocytes and a subset of B cells: molecular homology to its human counterpart Leu-1/T1 (CD5). Proc Natl Acad Sci U S A. 1987 Jan;84(1):204–208. doi: 10.1073/pnas.84.1.204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kearney J. F., Cooper M. D., Klein J., Abney E. R., Parkhouse R. M., Lawton A. R. Ontogeny of Ia and IgD on IgM-bearing B lymphocytes in mice. J Exp Med. 1977 Jul 1;146(1):297–301. doi: 10.1084/jem.146.1.297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kemp D. J., Harris A. W., Adams J. M. Transcripts of the immunoglobulin C mu gene vary in structure and splicing during lymphoid development. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7400–7404. doi: 10.1073/pnas.77.12.7400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kemp D. J., Harris A. W., Cory S., Adams J. M. Expression of the immunoglobulin C mu gene in mouse T and B lymphoid and myeloid cell lines. Proc Natl Acad Sci U S A. 1980 May;77(5):2876–2880. doi: 10.1073/pnas.77.5.2876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Levitt D., Cooper M. D. Mouse pre-B cells synthesize and secrete mu heavy chains but not light chains. Cell. 1980 Mar;19(3):617–625. doi: 10.1016/s0092-8674(80)80038-9. [DOI] [PubMed] [Google Scholar]
  29. Marcu K. B., Banerji J., Penncavage N. A., Lang R., Arnheim N. 5' flanking region of immunoglobulin heavy chain constant region genes displays length heterogeneity in germlines of inbred mouse strains. Cell. 1980 Nov;22(1 Pt 1):187–196. doi: 10.1016/0092-8674(80)90167-1. [DOI] [PubMed] [Google Scholar]
  30. Muller-Sieburg C. E., Whitlock C. A., Weissman I. L. Isolation of two early B lymphocyte progenitors from mouse marrow: a committed pre-pre-B cell and a clonogenic Thy-1-lo hematopoietic stem cell. Cell. 1986 Feb 28;44(4):653–662. doi: 10.1016/0092-8674(86)90274-6. [DOI] [PubMed] [Google Scholar]
  31. Nelson K. J., Haimovich J., Perry R. P. Characterization of productive and sterile transcripts from the immunoglobulin heavy-chain locus: processing of micron and muS mRNA. Mol Cell Biol. 1983 Jul;3(7):1317–1332. doi: 10.1128/mcb.3.7.1317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Paige C. J., Kincade P. W., Ralph P. Murine B cell leukemia line with inducible surface immunoglobulin expression. J Immunol. 1978 Aug;121(2):641–647. [PubMed] [Google Scholar]
  33. Piechaczyk M., Blanchard J. M., Marty L., Dani C., Panabieres F., El Sabouty S., Fort P., Jeanteur P. Post-transcriptional regulation of glyceraldehyde-3-phosphate-dehydrogenase gene expression in rat tissues. Nucleic Acids Res. 1984 Sep 25;12(18):6951–6963. doi: 10.1093/nar/12.18.6951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Pierce J. H., Aaronson S. A. BALB- and Harvey-murine sarcoma virus transformation of a novel lymphoid progenitor cell. J Exp Med. 1982 Sep 1;156(3):873–887. doi: 10.1084/jem.156.3.873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Pierce J. H., Aaronson S. A. Myeloid cell transformation by ras-containing murine sarcoma viruses. Mol Cell Biol. 1985 Apr;5(4):667–674. doi: 10.1128/mcb.5.4.667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Polla B. S., Poljak A., Geier S. G., Nathenson S. G., Ohara J., Paul W. E., Glimcher L. H. Three distinct signals can induce class II gene expression in a murine pre-B-cell line. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4878–4882. doi: 10.1073/pnas.83.13.4878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Polla B. S., Poljak A., Ohara J., Paul W. E., Glimcher L. H. Regulation of class II gene expression: analysis in B cell stimulatory factor 1-inducible murine pre-B cell lines. J Immunol. 1986 Nov 15;137(10):3332–3337. [PubMed] [Google Scholar]
  38. Shen F. W., Saga Y., Litman G., Freeman G., Tung J. S., Cantor H., Boyse E. A. Cloning of Ly-5 cDNA. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7360–7363. doi: 10.1073/pnas.82.21.7360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Stong R. C., Korsmeyer S. J., Parkin J. L., Arthur D. C., Kersey J. H. Human acute leukemia cell line with the t(4;11) chromosomal rearrangement exhibits B lineage and monocytic characteristics. Blood. 1985 Jan;65(1):21–31. [PubMed] [Google Scholar]
  40. Tung J. S., Scheid M. P., Pierotti M. A., Hämmerling U., Boyse E. A. Structural features and selective expression of three Ly-5+ cell-surface molecules. Immunogenetics. 1981;14(1-2):101–106. doi: 10.1007/BF00344303. [DOI] [PubMed] [Google Scholar]
  41. 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