Klaus S J, Phillips N E, Parker D C
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655.
Mol Immunol. 1993 Nov;30(16):1553-8. doi: 10.1016/0161-5890(93)90463-l.
Egr-1 is an immediate early gene that is rapidly upregulated in response to mitogenic signals induced by antigen receptor crosslinking on murine B lymphocytes. It has been shown that levels of Egr-1 expression are closely correlated with B cell proliferation in several models of B cell activation and tolerance. We compared the expression of Egr-1 during B cell stimulation with Fab'2 and IgG anti-immunoglobulin (anti-Ig), since it is known that Fab'2 anti-Ig is mitogenic while IgG anti-Ig is not, owing to a dominant inhibitory effect of crosslinking the B cell Fc gamma RII to membrane Ig. While mitogenic doses of Fab'2 anti-Ig induce large and rapid increases in Egr-1 expression, IgG anti-Ig results in smaller increases in Egr-1 mRNA, comparable to that seen with submitogenic concentrations of Fab'2 anti-Ig. However, the correlation between Egr-1 expression and B cell proliferation breaks down when IL-4 is added as a co-mitogen to induce B cell proliferation with IgG anti-Ig or submitogenic concentrations of Fab'2 anti-Ig. No corresponding increases in Egr-1 mRNA levels are observed when IL-4 is added. Therefore, IL-4 overcomes Fc receptor-mediated inhibition of B cell proliferation without affecting inhibition of Egr-1 mRNA induction, as demonstrated earlier for c-myc mRNA in this system.
Egr-1是一种即刻早期基因，在鼠B淋巴细胞上因抗原受体交联诱导的促有丝分裂信号作用下会迅速上调表达。在几种B细胞活化和耐受模型中，已表明Egr-1的表达水平与B细胞增殖密切相关。我们比较了用Fab'2和IgG抗免疫球蛋白（抗Ig）刺激B细胞期间Egr-1的表达情况，因为已知Fab'2抗Ig具有促有丝分裂作用，而IgG抗Ig则不然，这是由于B细胞FcγRII与膜Ig交联产生的显性抑制作用。虽然促有丝分裂剂量的Fab'2抗Ig会导致Egr-1表达大幅快速增加，但IgG抗Ig导致Egr-1 mRNA的增加较小，与亚促有丝分裂浓度的Fab'2抗Ig所观察到的情况相当。然而，当加入IL-4作为共刺激原与IgG抗Ig或亚促有丝分裂浓度的Fab'2抗Ig一起诱导B细胞增殖时，Egr-1表达与B细胞增殖之间的相关性就会消失。加入IL-4时未观察到Egr-1 mRNA水平相应增加。因此，IL-4克服了Fc受体介导的对B细胞增殖的抑制作用，而不影响对Egr-1 mRNA诱导的抑制，正如该系统中先前对c-myc mRNA所证明的那样。
