Transgenic mice selectively lacking MHC class II (I-E) antigen expression on B cells: an in vivo approach to investigate Ia gene function.
The E alpha MHC class II gene with 1.4 kb of 5'-flanking and 0.5 kb of 3'-flanking sequences was introduced into (H-2b X s)F2 mice, which do not express their endogenous E alpha gene. The transgene was expressed in thymic tissue and in adherent spleen cells and was induced in peritoneal exudate cells by gamma-interferon. In contrast to the normal E alpha gene, there was no expression in B lymphocytes. Since transgenic animals made with constructs containing 3.2 kb and 2 kb of 5'-flanking sequences show normal expression pattern of the E alpha gene, it appears that deletion of 5'-flanking sequences between -1.4 kb and -2 kb inactivated or eliminated regulatory sequences required for expression of E alpha specifically in B cells. The presence of pBR327 DNA linked to the -1.4 kb E alpha transgene suppresses expression in peripheral adherent cells, yielding mice expressing E alpha only in the thymus. These mice appear to be tolerant to I-E, as measured in mixed leukocyte response experiments.
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002872:Chromosome Deletion; D004742:Enhancer Elements, Genetic; D005796:Genes; D005822:Genetic Vectors; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D010957:Plasmids; D014176:Protein Biosynthesis; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology
D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen