Abstract
EARLY B-cell factor (EBF) is a cell type-specific transcription factor that is expressed at all antigen-independent stages of B-lym-phocyte differentiation and participates in the regulation of the mb-1 gene1á¤-4. Here we show, by targeted gene disruption in mice, that EBF is necessary for the generation of immunoglobulin-expressing B cells. EBF-deficient mice lack B cells that have rearranged their immunoglobulin D and JH gene segments, but contain B220+CD43+ progenitor cells that express germline áµ and IL-7 receptor transcripts. Various non-lymphoid tissues that express EBF are apparently normal in homozygous mutant mice, including olfactory neurons in which EBF was identified as Olf-1 (refs 5, 6). Together, these data suggest that EBF plays a specific and important role in the transcriptional control of B-cell differentiation at a stage before Ig (immunoglobulin) gene rearrangement but after commitment of cells to the B-lymphoid lineage.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Hagman, J., Travis, A. & Grosschedl, R. EMBO J. 10, 3409–3417 (1991).
Feldhaus, A. L., Mbangkollo, D., Arvin, K. L., Klug, C. A. & Singh, H. Molec. cell. Biol. 12, 1126–1133 (1992).
Travis, A., Hagman, J., Hwang, L. & Grosschedl, R. Molec. cell. Biol. 13, 3392–3400 (1993).
Hagman, J., Belanger, C., Travis, A., Turck, C. W. & Grosschedl, R. Genes Dev. 7, 760–773 (1993).
Wang, M. M. & Reed, R. R. Nature 364, 121–126 (1993).
Kudrycki, K. et al. Molec. cell. Biol. 13, 3002–3014 (1993).
Sakaguchi, N., Kashiwamura, S.-I., Kimoto, M., Thalmann, P. & Melchers, F. EMBO J. 7, 3457–3464 (1988).
Hombach, J., Tsubata, T., Leclercq, L., Stappert, H. & Reth, M. Nature 343, 760–762 (1990).
Campbell, K. S. & Cambier, J. C. EMBO J. 9, 441–448 (1990).
Venkitaraman, A. R., Williams, G. T., Dariavach, P. & Neuberger, M. S. Nature 352, 777–781 (1991).
Hagman, J., Gutch, M. J., Lin, H. & Grosschedl, R. EMBO J. 14, 2907–2916 (1995).
Milatovich, A., Qiu, R. G., Grosschedl, R. & Francke, U. Mammalian Genome 5, 211–215 (1994).
Kantor, A. B. & Herzenberg, L. A. A. Rev. Immun. 11, 501–538 (1993).
Rolink, A. & Melcher, F. Curr. Opin. Immun. 5, 207–217 (1993).
Hardy, R. R., Carmack, C. E., Shinton, S. A., Kemp, J. D. & Hayakawa, K. J. exp. Med. 173, 1213–1225 (1991).
Ehlich, A., Schaal, S., Gu, H., Kitamura, D., Muller, W. & Rajewsky, K. Cell 72, 695–704 (1993).
Li, Y. S., Hayakawa, K. & Hardy, R. R. J. exp. Med. 178, 951–960 (1993).
Schlissel, M. S., Voronova, A. & Baltimore, D. Genes Dev. 5, 1367–1376 (1991).
Mombaerts, P. et al. Cell 68, 869–877 (1992).
Shinkai, Y. et al. Cell 68, 855–867 (1992).
Spanopoulou, E. et al. Genes Dev. 8, 1030–1042 (1994).
Young, F. et al. Genes Dev. 8, 1043–1057 (1994).
Zhuang, Y., Soriano, P. & Weintraub, H. Cell 79, 875–884 (1994).
Bain, G. et al. Cell 79, 885–892 (1994).
Urbanek, P., Wang, Z. Q., Fetka, I., Wagner, E. F. & Busslinger, M. Cell 79, 901–912 (1994).
Scott, E. W., Simon, M. C., Anastasi, J. & Singh, H. Science 265, 1573–1577 (1994).
Georgopoulos, K. et al. Cell 79, 143–156 (1994).
Hunt, C. R., Ro, J. H., Dobson, D. E., Min, H. Y. & Spiegelman, B. M. Proc. natn. Acad. Sci. U.S.A. 83, 3786–3790 (1986).
Ramirez-Solis, R., Davis, A. C. & Bradley, A. Meth. Enzym. 255, 855–877 (1993).
Schlissel, M. S. & Baltimore, D. Cell 58, 1001–1007 (1989).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lin, H., Grosschedl, R. Failure of B-cell differentiation in mice lacking the transcription factor EBF. Nature 376, 263–267 (1995). https://doi.org/10.1038/376263a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/376263a0
This article is cited by
-
A landscape of gene expression regulation for synovium in arthritis
Nature Communications (2024)
-
Loss of SIRT1 inhibits hematopoietic stem cell aging and age-dependent mixed phenotype acute leukemia
Communications Biology (2022)
-
Pioneer factors as master regulators of the epigenome and cell fate
Nature Reviews Molecular Cell Biology (2022)
-
Identification of mutations that cooperate with defects in B cell transcription factors to initiate leukemia
Oncogene (2021)
-
Regeneration of immunocompetent B lymphopoiesis from pluripotent stem cells guided by transcription factors
Cellular & Molecular Immunology (2021)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.