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 f or murine AIDS (MAIDS) induces B-cell activation, proliferation, and differ entiation, including immunoglobulin class switch-recombination to immunoglo bulin E (IgE). Secretion of IgE normally requires the serial induction of i nterleukin 4 (IL-4), engagement of the IL-4 receptor, activation of signal transducer and activator of transcription (STAT) 6, and induction of IE ger mline transcripts as a prelude to switching. Remarkably, expression of IgE is equivalent in normal and IL-l-deficient mice with MAIDS (Morawetz et al. , a. Exp. Med. 184:1651-1661, 1996). To understand this anomaly, we studied mice with a null mutation of STAT6. Lymphoproliferation and immunodeficien cy, the hallmarks of MAIDS, developed with comparable kinetics and degree i n normal and mutant mice. In addition, serum IgE levels were indistinguisha ble in mice of either genotype. We conclude that B cells from mice with MAI DS activate unique IL-4- and STAT6-independent signaling pathways for B-cel l activation and differentiation.