Suv39h1/LSF对IgA肾病人腭扁桃体细胞IgA类别转换及低糖基化IgA1生成机制研究

IgA肾病是最常见原发性肾小球疾病。以IgA1/低糖基化IgA1沉积于肾小球为病理特征。IgA肾病人腭扁桃体细胞低糖基化IgA1增多，与肾小球沉积高度一致。研究发现：Suv39h1可促进Sμ-Sα重组，不依赖αGLT而增加IgA类别转换；LSF可结合Sμ-Sα序列，不影响αGLT而抑制IgA类别转换。Suv39h1和 LSF之间关系未明。我们推测：Suv39h1通过抑制LSF来促进IgA类别转换；Suv39h1在促进IgA类别转换同时，抑制β1，3半乳糖转移酶及分子伴侣Cosmc基因转录，或沉默LSF基因使该酶及Cosmc表达下调，致低糖基化IgA1增多。我们拟以IgA肾病人腭扁桃体细胞为研究平台；从组蛋白甲基化及乙酰化入手；采用免疫组化、磁珠分离、Western blot、免疫共沉淀、PCR和基因沉默及过表达等技术；探索Suv39h1/LSF对IgA类别转换及低糖基化IgA1生成机制。

IgA nephropathy(IgAN) is the most common form of primary glomerulonephritis, and the deposits of IgA/under-glycosylated IgA1 in glomerular mesangial area and/or capillary loops are the defining hallmark of the disease. The under-glycosylated IgA1 is elevated in the palatine tonsil cells of IgA nephropathy patients and it is highly coincident with the deposits in the glomeruli. Researchers have reported that Suv39h1 can induce Sμ-Sα recombination and increase the IgA class switching without depending on αGLT. LSF could combine with the Sμ-Sα sequence and repress IgA class switching without affecting αGLT. The relationship between Suv39h1 and LSF is unclear. We speculate that Suv39h1 could induce IgA class switching by repressing LSF, and increase under-glycosylated IgA1 by repressing the transcription of β1,3-galactosyltransferase and Cosmc or by silencing the gene of LSF to downregulate the expression of β1,3-galactosyltransferase and Cosmc. In this study，we intend to focus on the mononuclear cells and CD19(+)B cells of palatine tonsil of IgA nephropathy patients, starting with the research of histone methylation and acetylation, and try to find out the mechanism of IgA class switching and under-glycosylated IgA1 generation induced by Suv39h1/LSF with the methods of immunohistochemical staining,immunomagnetic beads,Western blot,co-immunoprecipitation,siRNA ，gene over-expression and RT-PCR.