Stimuli that enhance IgA class switching increase histone 3 acetylation at S alpha, but poorly stimulate sequential switching from IgG2b
Department of Molecular Genetics and Microbiology
Acetylation; Animals; Antibodies, Anti-Idiotypic; B-Cell Activating Factor; B-Lymphocytes; Cells, Cultured; Dextrans; Histones; Humans; Immunoglobulin A; Immunoglobulin Class Switching; Immunoglobulin G; Immunoglobulin Isotypes; Interleukin-4; Interleukin-5; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Spleen; Up-Regulation
Life Sciences | Medicine and Health Sciences | Women's Studies
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 (alpha delta Dex). To determine the mechanism of this increase, we asked whether IgA class switching correlates with acetylation of histone 3 at S alpha, the switch region for IgA. In the presence of the survival factor B lymphocyte stimulator (BLyS), acetylated histone 3 (AcH3) at S alpha was changed little by TGF-beta in LPS-stimulated mouse splenic B cell cultures, despite induction of GL alpha RNA. Compared with BLyS/LPS/TGF-beta alone, treatment with BLyS/LPS/TGF-beta/IL-4/IL-5/alpha delta Dex increased AcH3 at S alpha fourfold, and also increased GL alpha 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/alpha delta Dex. 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/ +/- alpha delta Dex. 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.
Rights and Permissions
Citation: Eur J Immunol. 2007 Jan;37(1):240-51. Link to article on publisher's site
Kaminski, Denise A. and Stavnezer, Janet, "Stimuli that enhance IgA class switching increase histone 3 acetylation at S alpha, but poorly stimulate sequential switching from IgG2b" (2007). Women’s Health Research Faculty Publications. 169.