Zitterkopf Nicole L, Jones Quentin A, Bradley David S, Durick Kelly, Rowland Raymond R, Plagemann Peter G W, Cafruny William A
Department of Basic Biomedical Sciences, University of South Dakota School of Medicine, Vermillion, South Dakota 57069, USA.
Viral Immunol. 2003;16(4):511-23. doi: 10.1089/088282403771926337.
Persistent infection of mice with lactate dehydrogenase-elevating virus (LDV) is associated with polyclonal B cell activation, autoimmunity, and circulating hydrophobic IgG-containing immune complexes (ICs), which bind to the surfaces of uncoated ELISA plates in the presence of 0.05% Tween 20. We demonstrate here that hydrophobic IgG-containing ICs also appear naturally in the plasma of autoimmune MRL/lpr mice. These and the similar hydrophobic ICs of LDV-infected mice as well as pigs coincide on ELISA plate surfaces with TGF-beta, apparently in the form of an IgG-TGF-beta complex. Circulating hydrophobic IgG-containing ICs are also susceptible to considerable amplification in vitro by exposure to alkaline conditions. By this latter method, the fraction of in vivo hydrophobic IgG, relative to the maximum in vitro chemically inducible IgG, was found to be about 20% in the plasma of LDV-infected mice, 5% in normal mouse plasma, and less than about 2% in pig plasma. These results indicate the potential for both chemically induced and protein-binding contributions to the generation of hydrophobic IgG-containing molecules, and have implications for immunopathological mechanisms in autoimmunity and persistent virus infections.
乳酸脱氢酶升高病毒(LDV)对小鼠的持续感染与多克隆B细胞活化、自身免疫以及循环中含疏水性IgG的免疫复合物(ICs)有关,这些免疫复合物在0.05%吐温20存在的情况下会结合到未包被的ELISA板表面。我们在此证明,含疏水性IgG的ICs也自然出现在自身免疫性MRL/lpr小鼠的血浆中。这些以及LDV感染小鼠和猪的类似疏水性ICs在ELISA板表面与TGF-β重合,显然是以IgG-TGF-β复合物的形式。循环中含疏水性IgG的ICs在体外暴露于碱性条件时也容易大量扩增。通过后一种方法,发现相对于体外化学诱导的最大IgG,体内疏水性IgG的比例在LDV感染小鼠的血浆中约为20%,在正常小鼠血浆中为5%,在猪血浆中小于约2%。这些结果表明化学诱导和蛋白质结合对含疏水性IgG分子生成的潜在贡献,并对自身免疫和持续性病毒感染中的免疫病理机制具有启示意义。