Holmdahl R, Bailey C, Enander I, Mayer R, Klareskog L, Moran T, Bona C
Department of Medical and Physiological Chemistry, Uppsala University, Sweden.
J Immunol. 1989 Mar 15;142(6):1881-6.
Autoantibodies play an important role in the pathogenesis of type II collagen-induced arthritis in mice. We have earlier reported a high frequency of cells producing anti-CII autoantibodies and a low frequency of cells producing multispecific antibodies, in regional lymph nodes 9 to 11 days after primary immunization with CII. It is shown here that anti-CII antibodies produced during primary immune response are IgG-antibodies mainly of IgG2a, IgG1 and IgG2b subclasses while IgM antibodies dominate primary responses elicited by OVA and denatured CII as analyzed with a large panel of hybridomas. Anti-CII antibodies generated during the primary response recognize at least five different epitopes on the CII molecule. The specificities of these antibodies for various epitopes result from combinational association of products encoded by genes derived from various VH and VK families and/or by the occurrence of somatic mutations. It is suggested that the primary anti-CII autoantibody response involves activation of memory B cells and is in this aspect different from the origin of "natural" autoantibodies.
自身抗体在小鼠Ⅱ型胶原诱导性关节炎的发病机制中起重要作用。我们之前报道过，在用Ⅱ型胶原进行初次免疫后9至11天，局部淋巴结中产生抗Ⅱ型胶原自身抗体的细胞频率较高，而产生多特异性抗体的细胞频率较低。本文显示，初次免疫反应期间产生的抗Ⅱ型胶原抗体主要是IgG抗体，主要为IgG2a、IgG1和IgG2b亚类，而用大量杂交瘤分析发现，IgM抗体在由卵清蛋白和变性Ⅱ型胶原引发的初次反应中占主导。初次反应期间产生的抗Ⅱ型胶原抗体识别Ⅱ型胶原分子上至少五个不同的表位。这些抗体对各种表位的特异性源于来自不同VH和VK家族的基因所编码产物的组合关联和/或体细胞突变的发生。有人提出，初次抗Ⅱ型胶原自身抗体反应涉及记忆B细胞的激活，在这方面与“天然”自身抗体的起源不同。
