Stimuli that enhance IgA class switching increase histone 3 acetylation at Sα, but poorly stimulate sequential switching from IgG2b

Abstract

Germ-line (GL) a transcription can be induced in mouse splenic B cells by LPS and TGF-β. This stimulation results in ∼ 1% IgA+ cells, which can be increased by IL-4, IL-5, and anti-IgD dextran (αδDex). To determine the mechanism of this increase, we asked whether IgA class switching correlates with acetylation of histone 3 at Sα, the switch region for IgA. In the presence of the survival factor B lymphocyte stimulator (BLyS), acetylated histone 3 (AcH3) at Sα. was changed little by TGF-β in LPS-stimulaed mouse splenic B cell cultures, despite induction of GLα, RNA. Compared with BLyS/LPS/TGF-β alone, treatment with BLyS/LPS/TGF-β/IL-4/IL-5/αδDex increased AcH3 at Sα fourfold, and also increased GLα RNA levels more than eightfold. By contrast, IgG2b class switching was optimal in BLyS/ LPS/TGF-β alone, and was suppressed by IL-4/IL-5/αδDex. 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-β/IL-4/IL-5/ ± αδDex. 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. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.