NOVEL IN-VITRO MODEL FOR HIGH-RATE IGA CLASS SWITCHING

The parameters necessary for induction of high-rate IgA class switchin g are unknown. Thus, although TGF-beta is a switch factor for the IgA class, the percentage of membrane (m)IgA(+) cells generated in vitro i n response to TGF-beta and various individual modes of B cell activati on 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 dete rmined 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 stimulat ion must occur in concert with multivalent Ag receptor crosslinking. A complex cytokine requirement is also revealed in that both IL-4 and I L-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 s uppresses the induction of mlgA(+) cells in response to these stimuli. This novel cellular system should serve as a powerful tool for studyi ng the molecular mechanisms that underly the IgA class switch and may provide insight into the physiologic parameters that induce it.