Ra. Morawetz et al., INTERLEUKIN (IL)-4-INDEPENDENT IMMUNOGLOBULIN CLASS SWITCH TO IMMUNOGLOBULIN (IG)E IN THE MOUSE, The Journal of experimental medicine, 184(5), 1996, pp. 1651-1661
Immunoglobulin (Ig) class switching in B cells is regulated by stimuli
transduced by cytokines and cell-cell contact. Among these stimuli, i
nterleukin (IL)-4 has been considered an absolute prerequisite for cla
ss switching to ISE in the mouse. Here we report that IL-4-deficient (
IL-4(-/-)) and wild-type mice had comparably elevated serum IgE levels
during the course of a murine retrovirus-induced immunodeficiency syn
drome, MAIDS. IgE switching in IL-4(-/-) mice was also induced by inje
ction of anti-IgD antibody. Treatment with anti-IgD induced germline e
psilon (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 low
er by a factor of 300 in IL-4(-/-) mice Bs compared with controls. Ind
uction of g epsilon after anti-IgD treatment of IL-4(-/-) mice was una
ffected by simultaneous treatment with monoclonal antibodies to IL-4 a
nd IL-4 receptor ol chain; Infection of IL-4(-/-) mice with Nippostron
gylus brasiliensis, a potent stimulus for IgE production, resulted in
induction of g epsilon transcripts; however, p epsilon transcripts wer
e barely detectable and serum IgE was not detected. These findings est
ablish a novel IL-4-independent pathway for IgE switching in the mouse
that is strongly activated in retroviral infection but weakly in nema
tode infection. This pathway appears to be dependent on distinct facto
rs that separately control induction of g epsilon transcription and sw
itch recombination to p epsilon.