Selective regulation of mature IgG1 transcription by CD86 and beta 2-adrenergic receptor stimulation.
Stimulation of CD86 and the beta(2)-adrenergic receptor (beta(2)AR) on a B cell, either alone or together, is known to increase the level of IgG1 protein produced by a CD40 ligand/IL-4-activated B cell. It is also known that the mechanism by which CD40 and IL-4R stimulation on a B cell increases the level of IgG1 protein is by increasing germline gamma 1 transcription, IgG1 class switching, and mature IgG1 transcription, while the molecular mechanism responsible for mediating the CD86- and beta(2)AR-induced effect remains unknown. In the present study using real-time PCR we show that the level of mature IgG1 transcription increases in CD40 ligand/IL-4-activated B cells following stimulation of either CD86 and/or beta(2)AR, and that this increase reflects the increase in IgG1 protein. Furthermore, we show that the CD86- and/or beta(2)AR-induced increase in mature IgG1 transcript is due to an increase in the rate of mature IgG1 transcription, as determined by nuclear run-on analysis. This effect is additive when both receptors are stimulated and is lost when B cells from CD86- and beta(2)AR-deficient mice are used. In contrast, the level of germline gamma 1 transcription, the stability of mature IgG1 transcript, the number of IgG1-positive B cells, and the number of IgG1-secreting B cells did not change. These results provide the first evidence that CD86 and/or beta(2)AR stimulation on a CD40 ligand/IL-4-activated B cell increases the level of IgG1 protein produced per cell by increasing the rate of mature IgG1 transcription.
Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Columbus, OH 43210, USA.
Joseph R
JR
Podojil
Virginia M
VM
Sanders
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D051940:B7-2 Antigen; D023201:CD40 Ligand / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012323:RNA Processing, Post-Transcriptional / Q000276:immunology; D020871:RNA Stability / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000276:immunology*
D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D011947:Receptors, Antigen, B-Cell; D023201:CD40 Ligand; D015847:Interleukin-4