Anti-mu antibody blocks LPS driven B cell differentiation by suppressing specific mRNAs.
High concentrations of anti-mu antibodies inhibit differentiation and increase proliferation of adult mouse splenic B cells stimulated by LPS. Cells from treated cultures express Ia antigens and on removal of anti-mu reexpress membrane IgM. They do not develop into plasmablasts secreting IgM. To investigate the mechanism of suppression we used Northern blots hybridized with cDNA probes to mu, kappa, J, and I-A beta chains to analyze RNAs in anti-mu suppressed and control cultures. Messenger RNAs for mu, kappa, and J chains but not I-A beta chain are diminished in anti-mu treated cells as compared to controls. Cells treated with anti-kappa antibodies have decreased mRNA levels for mu as well as kappa chains. Suppression mediated by modulation of the IgM receptor is not immunologically specific, but selectively inhibits expression of a cluster of unlinked genes which are coordinately activated during differentiation.
Flahart
R E
RE
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232.
Lawton
A R
AR
D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D005260:Female; D000949:Histocompatibility Antigens Class II; D007075:Immunoglobulin M / Q000378:metabolism; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis / Q000235:genetics; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
D000888:Antibodies, Anti-Idiotypic; D000949:Histocompatibility Antigens Class II; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D008070:Lipopolysaccharides; D012333:RNA, Messenger