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

doi:10.1084/jem.184.5.1651

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

RA Morawetz, L Gabriele, LV Rizzo, N Noben-Trauth, R Kuhn, K Rajewsky, W Muller, TM Doherty, F Finkelman, RL Coffman and HC Morse 3rd
Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

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 wildtype mice had comparably elevated serum IgE levels during the course of a murine retrovirus-induced immunodeficiency syndrome, MAIDS. IgE switching in IL-4-/- mice was also induced by injection of anti-IgD antibody. Treatment with anti-IgD induced germline epsilon (g epsilon) transcripts with comparable efficiency in IL-4-/- mice and controls, but the levels of productive epsilon transcripts (p epsilon) 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 g epsilon after anti-IgD treatment of IL-4-/- mice was unaffected by simultaneous treatment with monoclonal antibodies to IL-4 and IL-4 receptor alpha chain. Infection of IL-4-/- mice with Nippostrongylus brasiliensis, a potent stimulus for IgE production, resulted in induction of g epsilon transcripts; however, p epsilon 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 g epsilon transcription and switch recombination to p epsilon.
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