Mechanism for transforming growth factor beta regulation of alpha mRNA in lipopolysaccharide-stimulated B cells.
Transforming growth factor (TGF)-beta has been shown to stimulate isotype switching to IgA in cultures of lipopolysaccharide (LPS)-stimulated B cells. The induction of isotype switching is associated with the appearance of novel germline alpha transcripts that cannot be found in cultures stimulated with LPS alone. TGF-beta also increases the steady state level of productive alpha mRNA. In order to further elucidate both the role of TGF-beta and germline transcripts in isotype switching to IgA in B cells, the mechanism responsible for the changes in alpha mRNA was investigated. The increase in alpha mRNA which does not occur until day 2 of culture continues until at least day 4. Nuclear run-on analysis demonstrated that TGF-beta does not significantly increase the rate of transcription of either germline or productive alpha mRNA after 12, 24, or 48 h of culture. However, by day 2 of culture TGF-beta increases the half-life of alpha mRNA. These findings support the idea that TGF-beta acts as a secondary signal to stimulate isotype switching to IgA in a population that has already received a signal that drives it toward IgA production. In addition these studies suggest that either the germline transcripts or processing of pre-germline alpha mRNA transcripts plays a role in targeting recombination.
Lebman
D A
DA
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond 23298.
Park
M J
MJ
Hansen-Bundy
S
S
Pandya
A
A
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D007070:Immunoglobulin A / Q000096:biosynthesis*; D017578:Immunoglobulin Class Switching / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
D007070:Immunoglobulin A; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta