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.
Podojil
Joseph R
JR
Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Columbus, OH 43210, USA.
Sanders
Virginia M
VM
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