| First Author | Santos JM | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 9164 |
| PubMed ID | 29907762 | Mgi Jnum | J:333279 |
| Mgi Id | MGI:6726708 | Doi | 10.1038/s41598-018-27448-4 |
| Citation | Santos JM, et al. (2018) Duplication of a germline promoter downstream of the IgH 3' regulatory region impairs class switch recombination. Sci Rep 8(1):9164 |
| abstractText | During an adaptive immune response, B cells can change their surface immunoglobulins from IgM to IgG, IgE or IgA through a process called class switch recombination (CSR). Switching is preceded by inducible non-coding germline transcription (GLT) of the selected constant gene(s), which is largely controlled by a super-enhancer called the 3' regulatory region (3'RR). Despite intense efforts, the precise mechanisms that regulate GLT are still elusive. In order to gain additional insights into these mechanisms, we analyzed GLT and CSR in mutant B cells carrying a duplication of the promoter of the alpha constant gene (Ialpha) downstream of 3'RR. Duplication of the Ialpha promoter affected differently GLT and CSR. While for most isotypes a drop in GLT was accompanied by a decrease in CSR, that was not the case for switching to IgA, which diminished despite unchanged GLT. Unexpectedly, there was no obvious effect on GLT and CSR to IgG3. Remarkably, specific stimuli that normally induce switching to IgG2b had contrasting effects in mutant B cells; Igamma2b was now preferentially responsive to the stimulus that induced Ialpha promoter. We propose that one mechanism underlying the induced 3'RR-mediated activation of GL promoters involves, at least in part, specific transcription factories. |
