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*Substance via MeSH
The Journal of Immunology, 2001, 167: 3257-3265.
Copyright © 2001 by The American Association of Immunologists

HS1,2 Enhancer Regulation of Germline {epsilon} and {gamma}2b Promoters in Murine B Lymphocytes: Evidence for Specific Promoter-Enhancer Interactions1

Jurga Laurencikiene2,*,{dagger}, Vilma Deveikaite*,{dagger} and Eva Severinson*

* Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden; and {dagger} Institute of Immunology, Vilnius, Lithuania

During an immune response, activated B cells develop into high rate Ig-secreting plasma cells. They also switch from production of IgM to IgG, IgA, or IgE. This process requires a DNA recombination event, which is regulated at the transcriptional level by the production of isotype-specific, sterile germline (GL) transcripts. Induction of these transcripts is controlled by GL promoters and, possibly, by IgH 3' enhancers. We investigated the interaction of the GL {epsilon} and {gamma}2b promoters with the HS1,2 enhancer using transiently transfected mouse primary B cells and cell lines. The constructs used for the transfections contained a GL promoter upstream and HS1,2 downstream of a luciferase reporter gene. Both GL {epsilon} and {gamma}2b promoters synergized strongly with the HS1,2 enhancer in activated primary B cells, a mature B cell line, and a plasma cell line. We show that the major activity of HS1,2 in activated primary B cells occurs within a 310-bp fragment that includes NF-{kappa}B, OCT, and NF of activated B cells (Ets/AP-1) sites. By mutating the consensus sequences for various transcription factors, we have determined which sites in HS1,2 are important for synergy with the GL {epsilon} and {gamma}2b promoters. Our findings indicate that different sites in HS1,2 might selectively interact with the GL {epsilon} and {gamma}2b promoters. We also provide evidence that B cell-specific activator protein is not an absolute suppressor of HS1,2 activity.




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