Increased expression of mXBP-1 (TREB-5) in thymic B cells in New Zealand mice

New Zealand Black mice as well as several other murine models of murine lup us are well known for premature degeneration of thymus and development of a utoimmunity. To focus on molecular events unique to murine lupus, we perfor med differential display using arbitrary primer pairs to distinguish NZB ve rsus BALB/c thymus at 5 weeks of age. Following an extensive analysis of DN A bands that were either consistently up or downregulated and from studies of expression pattern of thymic genes by in situ nucleic acid hybridization , we focused on one clone that was consistently differentially expressed be tween NZB and BALB/c thymus. This clone was isolated, sequenced, and identi fied as the murine homologue of the human X box binding protein (hXBP-1), a lso known as TREE 5. mXBP-1 was found to be consistently upregulated in B c ells in the thymic cortex of NZB and (NZB xNZW)F1, but not BALB/c, C3H/HeJ or C57BL/6 mice. Ln addition, it was dramatically elevated in MRL/lpr but n ot MRL/++ mice; similarly, it was increased in BXSB/Yaa male but not BXSB f emale thymic cortex. Of particular interest was an absence of mXBP-1 expres sion in the thymus of NZB/ Bln-Igh6(null) homozygotes. mXBP-1 has several p utative functions, including the regulation of MHC class II expression and by virtue of its ability to recognize CRE-like elements shown to be involve d in HTLV-1 transcription. (C) 2001 Academic Press.