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Gururajan M , Simmons A , Dasu T , Spear BT , Calulot C , Robertson DA , Wiest DL , Monroe JG , Bondada S
Early growth response genes regulate B cell development, proliferation, and immune response
Journal of Immunology. 2008 Oct;181(7) :4590-4602
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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-l(-/-) mice. Marginal zone 13 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 Ear 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.
Notes
Gururajan, Murali Simmons, Alan Dasu, Trivikram Spear, Brett T. Calulot, Christopher Robertson, Darrell A. Wiest, David L. Monroe, John G. Bondada, Subbarao AMER ASSOC IMMUNOLOGISTS 356CG