STAT6-deficient mice exhibit normal induction of murine AIDS and expression of immunoglobulin E following infection with LP-BM5 murine leukemia viruses.
The unique Gag polyprotein of the replication-defective virus responsible for murine AIDS (MAIDS) induces B-cell activation, proliferation, and differentiation, including immunoglobulin class switch-recombination to immunoglobulin E (IgE). Secretion of IgE normally requires the serial induction of interleukin 4 (IL-4), engagement of the IL-4 receptor, activation of signal transducer and activator of transcription (STAT) 6, and induction of Iepsilon germline transcripts as a prelude to switching. Remarkably, expression of IgE is equivalent in normal and IL-4-deficient mice with MAIDS (Morawetz et al., J. Exp. Med. 184:1651-1661, 1996). To understand this anomaly, we studied mice with a null mutation of STAT6. Lymphoproliferation and immunodeficiency, the hallmarks of MAIDS, developed with comparable kinetics and degree in normal and mutant mice. In addition, serum IgE levels were indistinguishable in mice of either genotype. We conclude that B cells from mice with MAIDS activate unique IL-4- and STAT6-independent signaling pathways for B-cell activation and differentiation.
Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. hmorse@atlas.niaid.nih.gov
H C
HC
Morse
T
T
McCarty
N A
NA
Giese
L
L
Taddesse-Heath
M J
MJ
Grusby
D000818:Animals; D007073:Immunoglobulin E / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000276:immunology; D009052:Leukemia Virus, Murine / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology*; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D007073:Immunoglobulin E