Lymphocyte-specific interferon regulatory factor (LSIRF) (now called IRF4) is a transcription factor expressed only in lymphocytes. Mice deficient in IRF4 showed normal distribution of B and T lymphocyes at 4 to 5 weeks of age but developed progressive generalized lymphadenopathy. IRF4-deficient mice exhibited a profound reduction in serum immunoglobulin concentrations and did not mount detectable antibody responses. T lymphocyte function was also impaired in vivo; these mice could not generate cytotoxic or antitumor responses. Thus, IRF4 is essential for the function and homeostasis of both mature B and mature T lymphocytes.
Interferon regulatory factor (IRF) genes encode a family of DNA-binding proteins that are involved in the transcriptional regulation of type-I interferon and/or interferon-inducible genes. We report here the characterization of LSIRF, a new member of the IRF gene family cloned from mouse spleen by the polymerase chain reaction using degenerate primers. LSIRF was found to encode a 51 kDa protein that shares a high degree of amino acid sequence homology in the DNA-binding domain with other IRF family members. LSIRF expression was detectable only in lymphoid cells. In contrast to other IRF genes, LSIRF expression was not induced by interferons, but rather by antigen-receptor mediated stimuli such as plant lectins, CD3 or IgM crosslinking. In in vitro DNA binding studies, LSIRF was able to bind to the interferon-stimulated response element (ISRE) of the MHC class I promoter. The expression pattern and DNA binding activities suggest that LSIRF plays a role in ISRE-targeted signal transduction mechanisms specific to lymphoid cells.
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