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EBF and Runx1 are required for B cell specific transcription and lineage identity
Author(s) -
Fields Scott Alan,
Lukin Kara L,
Månsson Robert,
Cherrier Marie,
Straign Desiree,
Speck Nancy A,
Grosschedl Rudolf,
Feeney Ann,
Sigvardsson Mikael,
Hagman James
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.350
Subject(s) - runx1 , b cell , cd19 , transcription factor , biology , lineage (genetic) , recombination activating gene , cell , haematopoiesis , microbiology and biotechnology , gene , stem cell , immunology , antibody , genetics , recombination
Transcription factors including Runx1 and Early B Cell Factor (EBF) are essential for B cell development. Hematopoiesis fails in the absence of Runx1, but its roles in B cells are largely unknown. B cell development is blocked at an early stage in the absence of EBF. Previously, we described the synergistic activation of the B cell‐specific mb‐1 promoter by EBF and Runx1. Here, we generated EBF‐Runx1 haploinsufficient (ERH) mice to study effects on B cell functions in vivo . B cell numbers were greatly reduced in bone marrow and spleens of ERH mice. DNA microarray analysis and qPCR detected changes in the expression of >100 genes. Frequencies of immunoglobulin light chain rearrangements were greatly reduced. Pre‐B cells of these mice also exhibited a partial loss of identity. A significant percentage of pre‐B cells of ERH mice expressed the NK cell markers NK1.1 and 2B4. Thus, in these mice the suppression of non‐B cell‐specific genes is relaxed. Intriguingly, B cells that expressed NK cell surface markers also expressed CD19, which is activated by Pax5 and is a marker of B cell lineage commitment. We propose that EBF and Runx1 synergistically activate the B cell lineage‐specific gene program, while suppressing other lineage programs. Our data support a recent model (Pongubala et al. 2007) implicating EBF in the control of B cell lineage commitment in addition to Pax5. Supported by NIH grants 2R01A1054661‐04A1 and T32AI07405.