The roles of IL-4, TGF-beta and LPS in IgA switching.
CH12.LX B cells have been used as a lymphoma model of MHC restricted, antigen-dependent B cell differentiation. These B cells express surface IgM and secrete IgM. Most recently we have demonstrated that CH12.LX is a model of cytokine driven IgA differentiation. Recently, transforming growth factor beta (TGF-beta) has been shown to be a probable switch factor for IgA in LPS-stimulated mouse lymphocytes, therefore we chose CH12.LX B cells to study the effect of IL-4, TGF-beta and LPS in IgA isotype switching. Adding TGF-beta to the monoclonal cell line CH12.LX results in induction of mIgA expression but no enhancement of IgA secretion similar to the effect of IL-4. The addition of LPS serves as a non-specific stimulus to enhance the secretion of the expressed immunoglobulin, but has no IgA specific activity of its own. IL-4 and TGF-beta together are synergistic for mIgA expression. Pretreatment studies show that TGF-beta added after IL-4 is the same as TGF-beta alone whereas the converse is the same as adding both cytokines together. TGF-beta acts by increasing the steady state levels of alpha message, whereas northern analysis indicates that IL-4 does not induce alpha message the way TGF-beta does. These data confirm that TGF-beta by itself is an isotype switch factor for IgA. In addition, IL-4 and TGF-beta cause mIgA expression through different mechanisms. CH12.LX B cells serve as a valuable model to study the role of multiple signals required for mIgA expression and IgA secretion.
Kunimoto
D Y
DY
Department of Medical Microbiology and Infectious Diseases, University of Alberta, Edmonton, Canada.
Ritzel
M
M
Tsang
M
M
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004357:Drug Synergism; D007070:Immunoglobulin A / Q000235:genetics / Q000378:metabolism*; D007134:Immunoglobulin Switch Region / Q000187:drug effects; D015847:Interleukin-4 / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*
D007070:Immunoglobulin A; D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta; D015847:Interleukin-4