Sequences associated with the mouse Smu switch region are important for immunoglobulin heavy chain transgene expression in B cell development.
Analyses of H-chain transgenes have indicated that sequences situated between the mu intronic enhancer and the Cmu exons are important for mu gene expression. We have analyzed several variant mu transgenes and find that a sequence element located within or just upstream of Smu is important for mu transgene expression in both immature and mature B cells. This Smu -associated element appears to be required for functional mu expression in small, resting pre-B cells but not in proliferating pre-B cells. Our results also indicate that this element is responsible for previously reported differential transgene expression in resting and activated/proliferating mature B cells. However, our studies of knockout mice show that deletion of the Smu -associated element from the endogenous IgH locus does not alter early B cell maturation. This indicates that other elements within the H-chain locus can replace the function of the Smu -associated element at least to the mature B cell stage. Surprisingly, we also find that Smu deletion in the IgH locus does not affect levels of the sterile germ-line mu transcripts that are involved in B cell class switching, even though S-region sequences have been indicated to be important for the production of analogous germ-line transcripts for other isotypes.
Luby
T M
TM
Immunology Program and Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA.
Sigurdardottir
D
D
Berger
E D
ED
Selsing
E
E
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D002874:Chromosome Mapping; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D017578:Immunoglobulin Class Switching; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D020080:Tandem Repeat Sequences; D014158:Transcription, Genetic; D019076:Transgenes
D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M