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* Department for Biomedicin and Surgery, Linköping University,
Department for Immunology, Lund University, and
Lund Strategic Center for Stem Cell Biology, Sweden
Development of B-lymphoid cells in the bone marrow is a process under strict control of a hierarchy of transcription factors. To understand the development of a B-lymphoid-restricted functional network of transcription factors, we have investigated the cell autonomous role of the transcription factor EBF1 in early B cell development. This revealed that even though transplanted EBF1-deficient fetal liver cells were able to generate common lymphoid progenitors (CLPs) as well as B220+CD43+AA4.1+ candidate precursor B cells, none of these populations showed signs of B lineage priming. The isolated CLPs were able to generate T lymphocytes in vitro supporting the idea that the phenotype of EBF1-deficient mice is restricted to the development of the B lineage. Furthermore, EBF deficient CLPs displayed a reduction in Ig H chain recombination as compared with their wild-type counterpart and essentially lacked transcription of B-lineage-associated genes. Among the genes displaying reduced expression in the EBF1 deficient CLPs were the transcription factors Pax5, Pou2af1 (OcaB), and FoxO1 that all appear to be direct genetic targets for EBF1 because their promoters contained functional binding sites for this factor. This leads us to suggest that EBF1 regulates a transcription factor network crucial for B lineage commitment.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 These studies were generously supported by grants from the Swedish Cancer Society, the Swedish Research Council, Tobias Stiftelsen, the Swedish Childhood Cancer Foundation, The Swedish Foundation for Strategic Research, and the faculty of Medicine at Linköping University.
R.M. and D.B. performed transplantation experiments and cell sorting while genomics and RNA analysis work was performed by S.Z. and R.M., S.Z., P.T., J.Z., and M.S. performed promoter analysis and transfection experiments. All authors contributed to the experimental design and were involved in the writing of the manuscript.
2 S.Z. and R.M. contributed equally to this study.
3 Address correspondence and reprint requests to Dr. Mikael Sigvardsson, Stemcell Center, Lund University, Laboratory for Cellular Differentiation, BMC B12, Lund, Sweden. E-mail address: mikael.sigvardsson{at}ibk.liu.se
4 Abbreviations used in this paper: KO, knockout; FL, fetal liver; PI, propidium iodine; BM, bone marrow; WT, wild type; CLP, common lymphoid progenitors; LMPP, lympho myeloid primed progenitors; Q-PCR, real-time quantitative PCR.
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