Increased Expression of mXBP-1 (TREB-5) in Thymic B Cells in New Zealand Mice

Abstract

New Zealand Black mice as well as several other murine models of murine lupus are well known for premature degeneration of thymus and development of autoimmunity. To focus on molecular events unique to murine lupus, we performed differential display using arbitrary primer pairs to distinguish NZB versus BALB/c thymus at 5 weeks of age. Following an extensive analysis of DNA bands that were either consistently up or downregulated and from studies of expression pattern of thymic genes byin situ nucleic acid hybridization, we focused on one clone that was consistently differentially expressed between NZB and BALB/c thymus. This clone was isolated, sequenced, and identified as the murine homologue of the human X box binding protein (hXBP-1), also known as TREB 5. mXBP-1 was found to be consistently upregulated in B cells in the thymic cortex of NZB and (NZB×NZW)F1, but not BALB/c, C3H/HeJ or C57BL/6 mice. In addition, it was dramatically elevated in MRL/ lpr but not MRL/++ mice; similarly, it was increased in BXSB/ Yaa male but not BXSB female thymic cortex. Of particular interest was an absence of mXBP-1 expression in the thymus of NZB/ Bln- Igh6nullhomozygotes. mXBP-1 has several putative functions, including the regulation of MHC class II expression and by virtue of its ability to recognize CRE-like elements shown to be involved in HTLV-1 transcription.