Immunoglobulin heavy chain enhancer

Mature B lymphocytes express AhR and ARNT,10,12 and the ability of TCDD to suppress primary antibody responses has been known for a long time (reviewed in4). While the precise mechanisms resulting in suppression of T-dependent B cell responses in vivo have not been fully elucidated, it is clear that direct effects of TCDD on B cells plays a role. Studies using two B cell lines with differential AhR expression have linked suppression of LPS-induced IgM production to AhR activation, and have shown that AhR interactions within the 3 alpha immunoglobulin heavy chain enhancer directly influence antibody production.52-54 TCDD also appears to directly modulate the expression of CD19 on human B cells, suggesting another mechanism by which TCDD down-modulates the responsiveness of mature B cells.55... 

Sulentic, C., et. al., Interactions at a dioxin responsive element (DRE) and an overlapping kappaB site within the hs4 domain of the 3 alpha immunoglobulin heavy chain enhancer, Toxicology, 200, 235, 2004. 

Kohwi-Shigematsu, T., and Kohwi, Y. (1990). Torsional stress stabilizes extended base unpairing in suppressor sites flanking immunoglobulin heavy chain enhancer. Biochemistry 29, 9551-9560. 

Libermann, T. A., Lenardo, M., and Baltimore, D. (1990). Involvement of a second lymphoid-specific enhancer element in the regulation of immunoglobulin heavy-chain gene expression. Mol. Cell. Biol. 10 3155-3162. 

A detailed functional analysis of the immunoglobulin promoter elements is not available. However, comparison of sequences from a number of immunoglobulin promoters revealed the presence of a well-conserved octanucleotide consensus (ATGCAAAT) in all VH promoters and its complement (ATTTGCAT) in all VL promoters as well as in the heavy chain enhancer [54,55], This octanucleotide has been shown to be essential for transcription in both VH and VK promoters, as deletion of it abolishes promoter activity [46,55,56]. Furthermore, in the presence of the IgH enhancer, the octanucleotide is a sufficient VH upstream promoter element as measured in transfection assays [57],... 

Cockerill, P. N., Yuen, M.-H., and Garrard, W. T. (1987). The enhancer of the immunoglobulin heavy chain locus is flanked by presumptive chromosomal loop anchorage elements. J. Biol. Chem. 262, 5394-5397. 

Banerji, J., Olson, L., and Schaffner, W., 1983, A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell 33 729-740. 

Gillies, S. D., Morrison, S. L., Oi, V. T., and Tonegawa, S., 1983, A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell 33 717-728. 

Mercola, M., Wang, X.-F., Olsen, J., and Calame, K., 1983, Transcriptional enhancer elements in the mouse immunoglobulin heavy chain locus. Science 221 663-665. 

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