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Publication : Ig synthesis and class switching do not require the presence of the hs4 enhancer in the 3' IgH regulatory region.

First Author  Vincent-Fabert C Year  2009
Journal  J Immunol Volume  182
Issue  11 Pages  6926-32
PubMed ID  19454689 Mgi Jnum  J:165617
Mgi Id  MGI:4837818 Doi  10.4049/jimmunol.0900214
Citation  Vincent-Fabert C, et al. (2009) Ig synthesis and class switching do not require the presence of the hs4 enhancer in the 3' IgH regulatory region. J Immunol 182(11):6926-32
abstractText  Several studies have reported that regulatory elements located 3' of the IgH locus (namely hs3a, hs1,2, hs3b, and hs4) might play a role during class switch recombination (CSR) and Ig synthesis. While individual deletion of hs3a or hs1,2 had no effect, pairwise deletion of hs3b (an inverted copy of hs3a) and hs4 markedly affected CSR and Ig expression. Among these two elements, hs4 was tentatively presented with the master role due to its unique status within the 3' regulatory region: distal position outside repeated regions, early activation in pre-B cells, strong activity throughout B cell ontogeny. To clarify its role, we generated mice with a clean deletion of the hs4 after replacement with a floxed neo(R) cassette. Surprisingly, and as for previous deletion of hs3a or hs1,2, deletion of hs4 did not affect either in vivo CSR or the secretion level of any Ig isotype. In vitro CSR and Ig secretion in response to LPS and cytokines was not affected either. The only noticeable effects of the hs4 deletion were a decrease in the number of B splenocytes and a decreased membrane IgM expression. In conclusion, while dispensable for CSR and Ig transcription in plasma cells, hs4 mostly appears to contribute to Ig transcription in resting B lymphocytes.
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