| First Author | Kaminski DA | Year | 2007 |
| Journal | Eur J Immunol | Volume | 37 |
| Issue | 1 | Pages | 240-51 |
| PubMed ID | 17163453 | Mgi Jnum | J:117065 |
| Mgi Id | MGI:3695530 | Doi | 10.1002/eji.200636645 |
| Citation | Kaminski DA, et al. (2007) Stimuli that enhance IgA class switching increase histone 3 acetylation at Salpha, but poorly stimulate sequential switching from IgG2b. Eur J Immunol 37(1):240-51 |
| abstractText | Germ-line (GL) alpha transcription can be induced in mouse splenic B cells by LPS and TGF-beta. This stimulation results in approximately 1% IgA(+) cells, which can be increased by IL-4, IL-5, and anti-IgD dextran (alphadeltaDex). To determine the mechanism of this increase, we asked whether IgA class switching correlates with acetylation of histone 3 at Salpha, the switch region for IgA. In the presence of the survival factor B lymphocyte stimulator (BLyS), acetylated histone 3 (AcH3) at Salpha was changed little by TGF-beta in LPS-stimulated mouse splenic B cell cultures, despite induction of GLalpha RNA. Compared with BLyS/LPS/TGF-beta alone, treatment with BLyS/LPS/TGF-beta/IL-4/IL-5/alphadeltaDex increased AcH3 at Salpha fourfold, and also increased GLalpha RNA levels more than eightfold. By contrast, IgG2b class switching was optimal in BLyS/LPS/TGF-beta alone, and was suppressed by IL-4/IL-5/alphadeltaDex. Thus, B cell activators that increase IgA class switching do not increase IgG2b class switching. Further investigation showed that in contrast to purified IgM(+) cells, IgG2b(+) cells switched poorly to IgA in response to BLyS/LPS/TGF-beta/IL-4/IL-5/ +/- alphadeltaDex. These results suggest that IgA class switching is unusual among isotypes in its requirement for multiple B cell activation signals in addition to LPS and the cytokine that initiates the corresponding GL transcription. |
