Novel in vitro model for high-rate IgA class switching.
The parameters necessary for induction of high-rate IgA class switching are unknown. Thus, although TGF-beta is switch factor for the IgA class, the percentage of membrane (m)IgA+ cells generated in vitro in response to TGF-beta and various individual modes of B cell activation is limited to 1 to 2% of the total B cell population, a percentage far below that observed within Peyer's patches. In this report we determined a set of parameters that act synergistically to generate up to 15 to 20% mIgA+ cells in vitro. A dual mode of B cell activation is required whereby signaling through CD40 or in response to LPS stimulation must occur in concert with multivalent Ag receptor crosslinking. A complex cytokine requirement is also revealed in that both IL-4 and IL-5 must be present with TGF-beta for high-rate IgA class switching to occur. By contrast, IFN-gamma, a known antagonist of IL-4, strongly suppresses the induction of mIgA+ cells in response to these stimuli. This novel cellular system should serve as a powerful tool for studying the molecular mechanisms that underly the IgA class switch and may provide insight into the physiologic parameters that induce it.
McIntyre
T M
TM
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814.
Kehry
M R
MR
Snapper
C M
CM
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand; D005260:Female; D005434:Flow Cytometry; D007070:Immunoglobulin A / Q000276:immunology*; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D016212:Transforming Growth Factor beta / Q000276:immunology*
D007070:Immunoglobulin A; D007132:Immunoglobulin Isotypes; D015848:Interleukin-5; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016212:Transforming Growth Factor beta; D023201:CD40 Ligand; D015847:Interleukin-4