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Bipotential B-macrophage progenitors are present in adult bone marrow

Abstract

According to the current model of adult hematopoiesis, differentiation of pluripotential hematopoietic stem cells into common myeloid- and lymphoid-committed progenitors establishes an early separation between the myeloid and lymphoid lineages. This report describes a rare and previously unidentified CD45RCD19+ B cell progenitor population in postnatal bone marrow that can also generate macrophages. In addition to the definition of this B-lineage intermediate, the data indicate that a developmental relationship between the B and macrophage lineages is retained during postnatal hematopoiesis.

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Figure 1: CD45R and CD19 expression in myeloid long-term cultures switched to lymphoid conditions and in primary BM cells.
Figure 2: Cell morphology, phenotype and immmunoglobulin gene rearrangement status of CD45RCD19+ BM cells.
Figure 3: CD45RCD19+ cells have B cell developmental potential.
Figure 4: CD45RCD19+ cells do not have T cell developmental potential.
Figure 5: CD45RCD19+ cells can generate macrophages.
Figure 6: CD45RCD19+ cells include bipotential B-macrophage progenitors.

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References

  1. Spangrude, G. J., Heimfeld, S. & Weissman, I. L. Purification and characterization of mouse hematopoietic stem cells. Science 241, 58–62 (1988).

    Article  CAS  Google Scholar 

  2. Ogawa, M. et al. Expression and function of c-kit in hemopoietic progenitor cells. J. Exp. Med. 174, 63–71 (1991).

    Article  CAS  Google Scholar 

  3. Phillips, R. A., Wu, D. D. & Fulop, G. M. Lymphoid-restricted stem cells. Curr. Top. Microbiol. Immunol. 141, 11–15 (1988).

    CAS  PubMed  Google Scholar 

  4. Akashi, K., Traver, D., Miyamoto, T. & Weissman, I. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 404, 193–197 (2000).

    Article  CAS  Google Scholar 

  5. Kondo, M., Weissman, I. & Akashi, K. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91, 661–672 (1997).

    Article  CAS  Google Scholar 

  6. Davidson, W. F., Pierce, J. H., Rudikoff, S. & Morse, H. C. D. Relationships between B cell and myeloid differentiation. Studies with a B lymphocyte progenitor line, HAFTL-1. J. Exp. Med. 168, 389–407 (1988).

    Article  CAS  Google Scholar 

  7. Cumano, A., Paige, C. J., Iscove, N. N. & Brady, G. Bipotential precursors of B cells and macrophages in murine fetal liver. Nature 356, 612–615 (1992).

    Article  CAS  Google Scholar 

  8. Kawamoto, H., Ohmura, K. & Katsura, Y. Direct evidence for the commitment of hematopoietic stem cells to T, B and myeloid lineages in murine fetal liver. Int. Immunol. 9, 1011–1019 (1997).

    Article  CAS  Google Scholar 

  9. Lacaud, G., Carlsson, L. & Keller, G. Identification of a fetal hematopoietic precursor with B cell, T cell and macrophage potential. Immunity 9, 827–838 (1998).

    Article  CAS  Google Scholar 

  10. Dzierzak, E. & Medvinsky, A. in Molecular Biology of B-cell and T-cell Development (eds. Monroe, J. & Rothenberg, E.) 3–26 (Humana Press, Totowa, 1990).

    Google Scholar 

  11. Greaves, M. F. et al. Lineage promiscuity in hemopoietic differentiation and leukemia. Blood 67, 1–11 (1986).

    CAS  PubMed  Google Scholar 

  12. Borrello, M. A. & Phipps, R. P. The B/Macrophage Cell - an Elusive Link between CD5+ B Lymphocytes and Macrophages. Immunol. Today 17, 471–475 (1996).

    Article  CAS  Google Scholar 

  13. Davidson, W. F., Pierce, J. H. & Holmes, K. L. Evidence for a developmental relationship between CD5+ B-lineage cells and macrophages. Ann. NY Acad. Sci. 651, 112–129 (1992).

    Article  CAS  Google Scholar 

  14. Hara, H., Sam, M., Maki, R., Wu, G. E. & Paige, C. Characterization of a 70Z/3 pre-B cell derived macrophage clone. Differential expression of Hox family genes. Int. Immunol. 2, 691–696 (1990).

    Article  CAS  Google Scholar 

  15. Martin, M. et al. A novel cellular model (SPGM 1) of switching between the pre-B cell and myelomonocytic lineages. J. Immunol. 150, 4395–4406 (1993).

    CAS  PubMed  Google Scholar 

  16. Katoh, S. et al. Conversion of normal Ly-1-positive B-lineage cells into Ly-1-positive macrophages in long-term bone marrow cultures. Dev. Immunol. 1, 113–125 (1990).

    Article  CAS  Google Scholar 

  17. Borrello, M. A. & Phipps, R. P. Fibroblasts support outgrowth of splenocytes simultaneously expressing B lymphocyte and macrophage characteristics. J. Immunol. 155, 4155–4161 (1995).

    CAS  PubMed  Google Scholar 

  18. Rolink, A. et al. A subpopulation of B220+ cells in murine bone marrow does not express CD19 and contains natural killer cell progenitors. J. Exp. Med. 183, 187–194 (1996).

    Article  CAS  Google Scholar 

  19. Li, Y., Wasserman, R., Hayakawa, K. & Hardy, R. R. Identification of the earliest B lineage stage in mouse bone marrow. Immunity 5, 527–535 (1996).

    Article  CAS  Google Scholar 

  20. Dexter, T., Allan, T. & Lajtha, L. Conditions controlling the proliferation of haematopoietic stem cells in vitro. J. Cell. Physiol. 91, 335–444 (1977).

    Article  CAS  Google Scholar 

  21. Whitlock, C. & Witte, O. Long-term culture of B lymphocytes and their precursors from murine bone marrow. Proc. Natl Acad. Sci. USA 79, 308–312 (1982).

    Article  Google Scholar 

  22. Dorshkind, K. In vitro differentiation of B lymphocytes from primitive hemopoietic precursors present in long-term bone marrow cultures. J. Immunol. 136, 422–429 (1986).

    CAS  PubMed  Google Scholar 

  23. Jordan, C., McKearn, J. & Lemischka, I. Cellular and developmental properties of fetal hematopoietic stem cells. Cell 61, 953–963 (1990).

    Article  CAS  Google Scholar 

  24. McKearn, J. P., Baum, C. & Davie, J. M. Cell surface antigens expressed by subsets of pre-B cells and B cells. J. Immunol. 132, 332–339 (1984).

    CAS  PubMed  Google Scholar 

  25. Hardy, R. R. et al. Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow. J. Exp. Med. 173, 1213–1225 (1991).

    Article  CAS  Google Scholar 

  26. Ledbetter, J. A. & Herzenberg, L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol. Rev. 47, 63–90 (1979).

    Article  CAS  Google Scholar 

  27. Moore, T. et al. Expression of CD43 on murine and human pluripotent hematopoietic stem cells. J.. Immunol. 153, 4978–4987 (1994).

    CAS  PubMed  Google Scholar 

  28. Wineman, J. P. et al. CD4 is expressed on murine pluripotent hematopoietic stem cells. Blood 80, 1717–1724 (1992).

    CAS  PubMed  Google Scholar 

  29. Miller, B. A., Antognetti, G. & Springer, T. A. Identification of cell surface antigens present on murine hematopoietic stem cells. J. Immunol. 134, 3286–3290 (1985).

    CAS  PubMed  Google Scholar 

  30. Hestdal, K. et al. Characterization and regulation of RB6-8C5 antigen expression on murine bone marrow cells. J. Immunol. 147, 22–28 (1991).

    CAS  PubMed  Google Scholar 

  31. Springer, T., Galfré, G., Secher, D. S. & Milstein, C. Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur. J. Immunol. 9, 301–306 (1979).

    Article  CAS  Google Scholar 

  32. Collins, L. S. & Dorshkind, K. A stromal cell line from myeloid long-term bone marrow cultures can support myelopoiesis and B lymphopoiesis. J. Immunol. 138, 1082–1087 (1987).

    CAS  PubMed  Google Scholar 

  33. Rolink, A. et al. Long-term proliferating early pre B cell lines and clones with the potential to develop to surface Ig–positive, mitogen reactive B cells in vitro and in vivo. EMBO J. 10, 327–336 (1991).

    Article  CAS  Google Scholar 

  34. Jenkinson, E. J., Franchi, L. L., Kingston, R. & Owen, J. J. Effect of deoxyguanosine on lymphopoiesis in the developing thymus rudiment in vitro: application in the production of chimeric thymus rudiments. Eur. J. Immunol. 12, 583–587 (1982).

    Article  CAS  Google Scholar 

  35. Williams, N. S. et al. Generation of lytic natural killer 1.1+, Ly-49 cells from multipotential murine bone marrow progenitors in a stroma-free culture: Definition of cytokine requirements and developmental intermediates. J. Exp. Med. 186, 1609–1614 (1997).

    Article  CAS  Google Scholar 

  36. Weilbaecher, K., Weissman, I., Blume, K. & Heimfeld, S. Culture of phenotypically defined hematopoietic stem cells and other progenitors at limiting dilution on Dexter monolayers. Blood 78, 945–952 (1991).

    CAS  PubMed  Google Scholar 

  37. Johnson, A. & Dorshkind, K. Stromal cells in myeloid and lymphoid long-term bone marrow cultures can support multiple hemopoietic lineages and modulate their production of hemopoietic growth factors. Blood 68, 1348–1354 (1986).

    CAS  PubMed  Google Scholar 

  38. Kelleher, P. & Knight, S. C. IL-12 increases CD80 expression and the stimulatory capacity of bone marrow-derived dendritic cells. Int. Immunol. 10, 749–755 (1998).

    Article  CAS  Google Scholar 

  39. Metlay, J. P. et al. The distinct leukocyte integrins of mouse spleen dendritic cells as identified with new hamster monoclonal antibodies. J. Exp. Med. 171, 1753–1771 (1990).

    Article  CAS  Google Scholar 

  40. Bjorck, P. & Kincade, P. W. CD19+ pro-B cells can give rise to dendritic cells in vitro. J. Immunol. 161, 5795–5799 (1998).

    CAS  PubMed  Google Scholar 

  41. Hombach, J. et al. Molecular components of the B-cell antigen receptor complex of the IgM class. Nature 343, 760–762 (1990).

    Article  CAS  Google Scholar 

  42. Kierney, P. C. & Dorshkind, K. B lymphocyte precursors and myeloid progenitors survive in diffusion chamber cultures but B cell differentiation requires close association with stromal cells. Blood 70, 1418–1424 (1987).

    CAS  PubMed  Google Scholar 

  43. Nutt, S. L., Heavey, B., Rolink, A. G. & Busslinger, M. Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature 401, 556–562 (1999).

    Article  CAS  Google Scholar 

  44. Kee, B. L. & Murre, C. Induction of early B cell factor (EBF) and multiple B lineage genes by the Basis helix-loop-helix transcription factor E12. J. Exp. Med. 188, 699–713 (1998).

    Article  CAS  Google Scholar 

  45. Wallin, J. J., Gackstetter, E. R. & Koshland, M. E. Dependence of BSAP repressor and activator functions on BSAP concentration. Science 279, 1961–1964 (1998).

    Article  CAS  Google Scholar 

  46. Nutt, S. L. et al. Independent regulation of the two Pax5 alleles during B-cell development. Nature Genet. 21, 390–395 (1999).

    Article  CAS  Google Scholar 

  47. Kantor, A. B. & Herzenberg, L. A. Origin of murine B cell lineages. Annu. Rev. Immunol. 11, 501–538 (1993).

    Article  CAS  Google Scholar 

  48. Tudor, K., Payne, K. J., Yamashita, Y. & Kincade, P. W. Functional assessment of precursors from murine bone marrow suggests a sequence of early B lineage differentiation events. Immunity 12, 335–345 (2000).

    Article  CAS  Google Scholar 

  49. Allman, D., Li, J. & Hardy, R. R. Commitment to the B lymphoid lineage occurs before DH–JH recombination. J. Exp. Med. 189, 735–740 (1999).

    Article  CAS  Google Scholar 

  50. Schlissel, M. S., Corcoran, L. M. & Baltimore, D. Virus-transformed pre-B cells show ordered activation but not inactivation of immunoglobulin gene rearrangement and transcription. J. Exp. Med. 173, 711–720 (1991).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank I. Williams for the Cell Sorter operation and G. Crooks and D. Rawlings for critical reading of the manuscript. Supported by the National Institutes of Health (HL60658). The Flow Cytometry Core Facility of the Jonsson Cancer Center is supported in part by the National Institutes of Health (CA16042).

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Correspondence to Kenneth Dorshkind.

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Montecino-Rodriguez, E., Leathers, H. & Dorshkind, K. Bipotential B-macrophage progenitors are present in adult bone marrow. Nat Immunol 2, 83–88 (2001). https://doi.org/10.1038/83210

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