Abstract
Egr-1 (early growth response gene-1) is an immediate early gene encoding a zinc finger motif-containing transcription factor. Upon cross-linking of BCR, mature B cells undergo proliferation with an increase in Egr-1 message. Immature B lymphoma cells that express Egr-1 message and protein constitutively are growth inhibited when Egr-1 is down-regulated by negative signals from BCR or by antisense oligonucleotides. To test the hypothesis that Egr-1 is important for B cell development, we examined B cells from primary and secondary lymphoid organs in Egr-1-/- mice. Marginal zone B cell development was arrested in these mice, whereas the B cells in all other compartments were increased. To test the hypothesis that Egr-1 function may be partially compensated by other Egr family members, we developed transgenic mice expressing a dominant negative form of Egr-1, which lacks the trans activation domain but retains the DNA-binding domain, in a B cell-specific manner. There was a decrease in B lymphopoiesis in the bone marrow accompanied by a reduction in splenic immature and mature B cells as well as marginal zone B cells in the transgenic mice. Moreover, transgenic mice respond poorly to BCR cross-linking in vitro and T-independent and T-dependent Ags in vivo.
Original language | English |
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Pages (from-to) | 4590-4602 |
Number of pages | 13 |
Journal | Journal of Immunology |
Volume | 181 |
Issue number | 7 |
DOIs | |
State | Published - Oct 1 2008 |
Keywords
- Animals
- Antigens, T-Independent/physiology
- B-Lymphocytes/cytology
- Cell Differentiation/genetics
- Cell Line
- Cell Line, Tumor
- Cell Proliferation
- Early Growth Response Protein 1/deficiency
- Female
- Lymphoid Tissue/cytology
- Lymphopoiesis/genetics
- Mice
- Mice, Inbred C3H
- Mice, Inbred C57BL
- Mice, Inbred CBA
- Mice, Knockout
- Mice, Transgenic
- Receptors, Antigen, B-Cell/physiology