Effects of IL-4 and Fc gamma receptor II engagement on Egr-1 expression during stimulation of B lymphocytes by membrane immunoglobulin crosslinking.
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.
Klaus
S J
SJ
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655.
Phillips
N E
NE
Parker
D C
DC
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D051766:Early Growth Response Protein 1; D015870:Gene Expression; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000302:isolation & purification; D017452:Receptors, IgG / Q000276:immunology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C080568:Fc gamma receptor IIA; D017874:Immediate-Early Proteins; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D012333:RNA, Messenger; D017452:Receptors, IgG; D014157:Transcription Factors; D015847:Interleukin-4