Abstract
The embryonic sites in which progenitors of the hematopoietic lineages first emerge are ideal regions to characterize both the cells and environment needed to initiate blood cell development. For a number of years both the murine yolk sac and embryo have been recognized to contain progenitors of B lymphocytes. However, clonal, quantitative in vitro assays, which allow precise observation of precursors and their progeny, have been lacking. Moreover, the site of origin of the initial events remains controversial. In this report we document the presence of B-cell progenitors in yolk sac and embryonic tissue obtained from mouse fetuses beginning at the 10-somite stage, day 8.5. We determine the frequency, cell-surface phenotype, and growth properties of these progenitors. We show that these cells can differentiate into immunoglobulin-secreting cells and that the progeny derived from single progenitors are diverse with respect to immunoglobulin heavy-chain allotype expression, diversity-joining region use, and heavy-chain variable-region utilization.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alt F. W., Blackwell T. K., Yancopoulos G. D. Development of the primary antibody repertoire. Science. 1987 Nov 20;238(4830):1079–1087. doi: 10.1126/science.3317825. [DOI] [PubMed] [Google Scholar]
- Andrew T. A., Owen J. J. Studies on the earliest sites of B cell differentiation in the mouse embryo. Dev Comp Immunol. 1978 Apr;2(2):339–346. doi: 10.1016/s0145-305x(78)80076-7. [DOI] [PubMed] [Google Scholar]
- Brodeur P. H., Osman G. E., Mackle J. J., Lalor T. M. The organization of the mouse Igh-V locus. Dispersion, interspersion, and the evolution of VH gene family clusters. J Exp Med. 1988 Dec 1;168(6):2261–2278. doi: 10.1084/jem.168.6.2261. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collins L. S., Dorshkind K. A stromal cell line from myeloid long-term bone marrow cultures can support myelopoiesis and B lymphopoiesis. J Immunol. 1987 Feb 15;138(4):1082–1087. [PubMed] [Google Scholar]
- Cumano A., Dorshkind K., Gillis S., Paige C. J. The influence of S17 stromal cells and interleukin 7 on B cell development. Eur J Immunol. 1990 Oct;20(10):2183–2189. doi: 10.1002/eji.1830201006. [DOI] [PubMed] [Google Scholar]
- Cumano A., Paige C. J. Enrichment and characterization of uncommitted B-cell precursors from fetal liver at day 12 of gestation. EMBO J. 1992 Feb;11(2):593–601. doi: 10.1002/j.1460-2075.1992.tb05091.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cumano A., Paige C. J., Iscove N. N., Brady G. Bipotential precursors of B cells and macrophages in murine fetal liver. Nature. 1992 Apr 16;356(6370):612–615. doi: 10.1038/356612a0. [DOI] [PubMed] [Google Scholar]
- Dieterlen-Lièvre F., Martin C. Diffuse intraembryonic hemopoiesis in normal and chimeric avian development. Dev Biol. 1981 Nov;88(1):180–191. doi: 10.1016/0012-1606(81)90228-1. [DOI] [PubMed] [Google Scholar]
- LeClair K. P., Palfree R. G., Flood P. M., Hammerling U., Bothwell A. Isolation of a murine Ly-6 cDNA reveals a new multigene family. EMBO J. 1986 Dec 1;5(12):3227–3234. doi: 10.1002/j.1460-2075.1986.tb04633.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McKearn J. P., McCubrey J., Fagg B. Enrichment of hematopoietic precursor cells and cloning of multipotential B-lymphocyte precursors. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7414–7418. doi: 10.1073/pnas.82.21.7414. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Melchers F. Murine embryonic B lymphocyte development in the placenta. Nature. 1979 Jan 18;277(5693):219–221. doi: 10.1038/277219a0. [DOI] [PubMed] [Google Scholar]
- Moore M. A., Metcalf D. Ontogeny of the haemopoietic system: yolk sac origin of in vivo and in vitro colony forming cells in the developing mouse embryo. Br J Haematol. 1970 Mar;18(3):279–296. doi: 10.1111/j.1365-2141.1970.tb01443.x. [DOI] [PubMed] [Google Scholar]
- Ogawa M., Nishikawa S., Ikuta K., Yamamura F., Naito M., Takahashi K., Nishikawa S. B cell ontogeny in murine embryo studied by a culture system with the monolayer of a stromal cell clone, ST2: B cell progenitor develops first in the embryonal body rather than in the yolk sac. EMBO J. 1988 May;7(5):1337–1343. doi: 10.1002/j.1460-2075.1988.tb02949.x. [DOI] [PMC free article] [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]
- Raff M. C., Megson M., Owen J. J., Cooper M. D. Early production of intracellular IgM by B-lymphocyte precursors in mouse. Nature. 1976 Jan 22;259(5540):224–226. doi: 10.1038/259224a0. [DOI] [PubMed] [Google Scholar]
- Reynaud C. A., Imhof B. A., Anquez V., Weill J. C. Emergence of committed B lymphoid progenitors in the developing chicken embryo. EMBO J. 1992 Dec;11(12):4349–4358. doi: 10.1002/j.1460-2075.1992.tb05534.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Solvason N., Lehuen A., Kearney J. F. An embryonic source of Ly1 but not conventional B cells. Int Immunol. 1991 Jun;3(6):543–550. doi: 10.1093/intimm/3.6.543. [DOI] [PubMed] [Google Scholar]
- Tyan M. L., Herzenberg L. A. Studies on the ontogeny of the mouse immune system. II. Immunoglobulin-producing cells. J Immunol. 1968 Sep;101(3):446–450. [PubMed] [Google Scholar]
- Wu G. E., Paige C. J. VH gene family utilization in colonies derived from B and pre-B cells detected by the RNA colony blot assay. EMBO J. 1986 Dec 20;5(13):3475–3481. doi: 10.1002/j.1460-2075.1986.tb04672.x. [DOI] [PMC free article] [PubMed] [Google Scholar]