| First Author | Bébin AG | Year | 2010 |
| Journal | J Immunol | Volume | 184 |
| Issue | 7 | Pages | 3710-7 |
| PubMed ID | 20176739 | Mgi Jnum | J:160101 |
| Mgi Id | MGI:4453418 | Doi | 10.4049/jimmunol.0901978 |
| Citation | Bebin AG, et al. (2010) In vivo redundant function of the 3' IgH regulatory element HS3b in the mouse. J Immunol 184(7):3710-7 |
| abstractText | In the mouse, the regulatory region located at the 3' end of the IgH locus includes four transcriptional enhancers: HS3a, HS1-2, HS3b, and HS4; the first three lie in a quasi-palindromic structure. Although the upstream elements HS3a and HS1-2 proved dispensable for Ig expression and class switch recombination (CSR), the joint deletion of HS3b and HS4 led to a consistent decrease in IgH expression in resting B cells and to a major CSR defect. Within this pair of distal enhancers, it was questionable whether HS3b and HS4 could be considered individually as elements critical for IgH expression and/or CSR. Studies in HS4-deficient mice recently revealed the role of HS4 as restricted to Igmicro-chain expression from the pre-B to the mature B cell stage and left HS3b as the last candidate for CSR regulation. Our present study finally invalidates the hypothesis that CSR could mostly rely on HS3b itself. B cells from HS3b-deficient animals undergo normal proliferation, germline transcription, and CSR upon in vitro stimulation with LPS; in vivo Ag-specific responses are not affected. In conclusion, our study highlights a major effect of the global ambiance of the IgH locus; enhancers demonstrated as being strongly synergistic in transgenes turn out to be redundant in their endogenous context. |
