Interleukin (IL)-4-independent immunoglobulin class switch to immunoglobulin (Ig)E in the mouse

Abstract

Immunoglobulin (Ig) class switching in B cells is regulated by stimuli transduced by cytokines and cell-cell contact. Among these stimuli, interleukin (IL)-4 has been considered an absolute prerequisite for class switching to IgE in the mouse. Here we report that IL-4-deficient (IL-4(-/- )) and wild-type mice bad comparably elevated serum IgE levels during the course of a murine retrovirus-reduced immunodeficiency syndrome, MAIDS. IgE switching in IL-4(-/-) mice was also induced by injection of anti-IgD antibody. Treatment with anti-IgD reduced germline epsilon (gε) transcripts with comparable efficiency in IL-4(-/-) mice and controls, but the levels of productive epsilon transcripts (pε) were lower by a factor of 200 and serum IgE levels were lower by a factor of 300 in IL-4(-/-) mice as compared with controls. Induction of gε after anti-IgD treatment of IL-4(-/-) mice was unaffected by simultaneous treatment with monoclonal antibodies to IL-4 and IL-4 receptor α chain. Infection of IL-4(-/-) mice with Nippostrongylus brasiliensis, a potent stimulus for IgE production, resulted in induction of gε transcripts; however, pε transcripts were barely detectable and serum IgE was not detected. These findings establish a novel IL-4-independent pathway for IgE switching in the mouse that is strongly activated in retroviral infection but weakly in nematode infection. This pathway appears to be dependent on distinct factors that separately control induction of gε transcription and switch recombination to pε.