Abstract
The emergence of functional B cells was monitored in irradiated or unirradiated CBA/N recipients of either adult bone marrow or fetal liver from CBA/HT6T6 donors. The cells that are primarily responsible for the generation of B lymphocytes, at least during the first 6 wk, are rapidly sedimenting (4.5-6 mm/h), lack surface immunoglobulin, and are found in both the adult bone marrow and the fetal liver from day 12 onward. These pre-B cells are distinct from the colony-forming unit spleen (CFU-s) as demonstrated by the following criteria: (a) absence from yolk sac (19), (b) lack of correlation between CFU-s number and the ability to generate B cells in fetal liver populations of different ages of gestation, and (c) hybridoma antibodies that significantly inhibited B cell reconstitution but have no effect on CFU-s numbers. The antigen detected by this antiserum is present on both the fetal liver and bone marrow B cell progenitor, although its expression is not restricted to the B lineage. The pre-B cells that we monitor are not homogeneous, however, as both physical and functional differences are found. These observations reinforce our thesis that committed progenitor cells for the humoral immune system are formed early in development and thereafter constitute the major precursor pool for the generation of B lymphocytes.
Full Text
The Full Text of this article is available as a PDF (699.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abramson S., Miller R. G., Phillips R. A. The identification in adult bone marrow of pluripotent and restricted stem cells of the myeloid and lymphoid systems. J Exp Med. 1977 Jun 1;145(6):1567–1579. doi: 10.1084/jem.145.6.1567. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burrows P. D., Kearney J. F., Lawton A. R., Cooper M. D. Pre-B cells: bone marrow persistence in anti-mu-suppressed mice, conversion to B lymphocytes, and recovery after destruction by cyclophosphamide. J Immunol. 1978 May;120(5):1526–1531. [PubMed] [Google Scholar]
- Gershon H., Feldman M. The immune reactivity of lymph node-derived spleen colonies and intercolonial cells. Immunology. 1969 Feb;16(2):175–185. [PMC free article] [PubMed] [Google Scholar]
- Harrison D. E. Competitive repopulation: a new assay for long-term stem cell functional capacity. Blood. 1980 Jan;55(1):77–81. [PubMed] [Google Scholar]
- Harrison D. E., Doubleday J. W. Normal function of immunologic stem cells from aged mice. J Immunol. 1975 Apr;114(4):1314–1317. [PubMed] [Google Scholar]
- Hellman S., Botnick L. E., Hannon E. C., Vigneulle R. M. Proliferative capacity of murine hematopoietic stem cells. Proc Natl Acad Sci U S A. 1978 Jan;75(1):490–494. doi: 10.1073/pnas.75.1.490. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hämmerling U., Chin A. F., Abbott J. Ontogeny of murine B lymphocytes: sequence of B-cell differentiation from surface-immunoglobulin-negative precursors to plasma cells. Proc Natl Acad Sci U S A. 1976 Jun;73(6):2008–2012. doi: 10.1073/pnas.73.6.2008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kearney J. F., Lawton A. R. B lymphocyte differentiation induced by lipopolysaccharide. II. Response of fetal lymphocytes. J Immunol. 1975 Sep;115(3):677–681. [PubMed] [Google Scholar]
- Kincade P. W. Defective colony formation by B lymphocytes from CBA/N and C3H/HeJ mice. J Exp Med. 1977 Feb 1;145(2):249–263. doi: 10.1084/jem.145.2.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kincade P. W., Lee G., Scheid M. P., Blum M. D. Characterization of murine colony-forming B cells. II. Limits to in vitro maturation, Lyb-2 expression, resolution of IgD+ subsets, and further population analysis. J Immunol. 1980 Feb;124(2):947–953. [PubMed] [Google Scholar]
- Kincade P. W., Moore M. A., Schlegel R. A., Pye J. B lymphocyte differentiation from fetal liver stem cells in89 Sr-treated mice1. J Immunol. 1975 Nov;115(5):1217–1222. [PubMed] [Google Scholar]
- 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]
- Kincade P. W., Ralph P., Moore M. A. Growth of B-lymphocytes clones in semisolid culture is mitogen dependent. J Exp Med. 1976 May 1;143(5):1265–1270. doi: 10.1084/jem.143.5.1265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lafleur L., Miller R. G., Phillips R. A. A quantitative assay for the progenitors of bone marrow-associated lymphocytes. J Exp Med. 1972 Jun 1;135(6):1363–1374. doi: 10.1084/jem.135.6.1363. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lafleur L., Underdown B. J., Miller R. G., Phillips R. A. Differentiation of lymphocytes: characterization of early precursors of B lymphocytes. Ser Haematol. 1972;5(2):50–63. [PubMed] [Google Scholar]
- Lala P. K., Johnson G. R., Battye F. L., Nossal G. J. Maturation of B lymphocytes. I. Concurrent appearance of increasing Ig, Ia, and mitogen responsiveness. J Immunol. 1979 Jan;122(1):334–341. [PubMed] [Google Scholar]
- Lala P. K., Johnson G. R. Monoclonal origin of B lymphocyte colony-forming cells in spleen colonies formed by multipotential hemopoietic stem cells. J Exp Med. 1978 Dec 1;148(6):1468–1477. doi: 10.1084/jem.148.6.1468. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lau C. Y., Melchers F., Miller R. G., Phillips R. A. In vitro differentiation of B lymphocytes from pre-B cells. J Immunol. 1979 Apr;122(4):1273–1277. [PubMed] [Google Scholar]
- Melchers F. B lymphocyte development in fetal liver. II. Frequencies of precursor B cells during gestation. Eur J Immunol. 1977 Jul;7(7):482–486. doi: 10.1002/eji.1830070715. [DOI] [PubMed] [Google Scholar]
- Metcalf D., Nossal G. J., Warner N. L., Miller J. F., Mandel T. E., Layton J. E., Gutman G. A. Growth of B-lymphocyte colonies in vitro. J Exp Med. 1975 Dec 1;142(6):1534–1549. doi: 10.1084/jem.142.6.1534. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Metcalf D., Warner N. L., Nossal G. J., Miller J. F., Shortman K., Rabellino E. Growth of B lymphocyte colonies in vitro from mouse lymphoid organs. Nature. 1975 Jun 19;255(5510):630–632. doi: 10.1038/255630a0. [DOI] [PubMed] [Google Scholar]
- Miller R. G., Phillips R. A. Separation of cells by velocity sedimentation. J Cell Physiol. 1969 Jun;73(3):191–201. doi: 10.1002/jcp.1040730305. [DOI] [PubMed] [Google Scholar]
- Nossal G. J., Pike B. L. Studies on the differentiation of B lymphocytes in the mouse. Immunology. 1973 Jul;25(1):33–45. [PMC free article] [PubMed] [Google Scholar]
- Osmond D. G., Nossal G. J. Differentiation of lymphocytes in mouse bone marrow. II. Kinetics of maturation and renewal of antiglobulin-binding cells studied by double labeling. Cell Immunol. 1974 Jul;13(1):132–145. doi: 10.1016/0008-8749(74)90233-0. [DOI] [PubMed] [Google Scholar]
- Owen J. J., Jordan R. K., Robinson J. H., Singh U., Willcox H. N. In vitro studies on the generation of lymphocyte diversity. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):129–137. doi: 10.1101/sqb.1977.041.01.017. [DOI] [PubMed] [Google Scholar]
- Owen J. J., Wright D. E., Habu S., Raff M. C., Cooper M. D. Studies on the generation of B lymphocytes in fetal liver and bone marrow. J Immunol. 1977 Jun;118(6):2067–2072. [PubMed] [Google Scholar]
- 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]
- 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]
- Phillips R. A., Melchers F. Appearance of functional lymphocytes in fetal liver. J Immunol. 1976 Oct;117(4):1099–1103. [PubMed] [Google Scholar]
- Rozing J., Benner R. The recovery of the B cell compartment in lethally irradiated and reconstituted mice. Adv Exp Med Biol. 1976;66:203–208. doi: 10.1007/978-1-4613-4355-4_31. [DOI] [PubMed] [Google Scholar]
- Scott D. W., Layton J. E., Johnson G. R. Surface immunoglobulin phenotype of murine spleen cells which form B cell colonies in agar. Eur J Immunol. 1978 Apr;8(4):286–288. doi: 10.1002/eji.1830080413. [DOI] [PubMed] [Google Scholar]
- Sherr D. H., Szewczuk M. R., Siskind G. W. Ontogeny of B-lymphocyte function. V. Thymus cell involvement in the functional maturation of B-lymphocytes from fetal mice transferred into adult irradiated hosts. J Exp Med. 1978 Jan 1;147(1):196–206. doi: 10.1084/jem.147.1.196. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shinefeld L. A., Sato V. L., Rosenberg N. E. Monoclonal rat anti-mouse brain antibody detects Abelson murine leukemia virus target cells in mouse bone marrow. Cell. 1980 May;20(1):11–17. doi: 10.1016/0092-8674(80)90229-9. [DOI] [PubMed] [Google Scholar]
- TILL J. E., McCULLOCH E. A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961 Feb;14:213–222. [PubMed] [Google Scholar]
- Trentin J. J. Determination of bone marrow stem cell differentiation by stromal hemopoietic inductive microenvironments (HIM). Am J Pathol. 1971 Dec;65(3):621–628. [PMC free article] [PubMed] [Google Scholar]
- Williams N., Jackson H. Regulation of proliferation of murine megakaryocyte progenitor cells by cell cycle. Blood. 1978 Jul;52(1):163–170. [PubMed] [Google Scholar]
- Wu A. M., Siminovitch L., Till J. E., McCulloch E. A. Evidence for a relationship between mouse hemopoietic stem cells and cells forming colonies in culture. Proc Natl Acad Sci U S A. 1968 Apr;59(4):1209–1215. doi: 10.1073/pnas.59.4.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yung L. L., Wyn-Evans T. C., Diener E. Ontogeny of the murine immune system: development of antigen recognition and immune responsiveness. Eur J Immunol. 1973 Apr;3(4):224–228. doi: 10.1002/eji.1830030409. [DOI] [PubMed] [Google Scholar]