Human rheumatoid factor cross-idiotypes. IV. Studies on WA XId-positive IgM without rheumatoid factor activity provide evidence that the WA XId is not unique to rheumatoid factors and is distinct from the 17.109 and G6 XIds.
Human rheumatoid factor cross-idiotypes. IV. Studies on WA XId-positive IgM without rheumatoid factor activity provide evidence that the WA XId is not unique to rheumatoid factors and is distinct from the 17.109 and G6 XIds.
复制标题
人类类风湿因子交叉独特型。
DOI：
10.1084/jem.178.6.1903
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Zhang,QX
中科院分区：
文献类型：
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作者：
Knight,GB;Agnello,V;Bonagura,V;Barnes,JL;Panka,DJ;Zhang,QX
Wa交叉独特型(XID)是人类类风湿因子(MRF)中的主要XID，几乎总是与轻链(L)XID(17.109)和重(H)链XID(G6)相关。克隆了一株具有WAXID的细胞系35G6，但与免疫球蛋白G无反应，对17.109和G6XId阴性。35G6 L链似乎与大多数WA MRF L链来自相同的VKIII-JKI基因。与使用VH1基因的WA MRFS H链不同，35G6 IgM表达VH3基因。与其他WAXID阳性的MRF的序列比较表明，几个共同的结构特征可能与WAXID有关，而差异可能与缺乏免疫球蛋白反应有关。此前，在正常人和类风湿性关节炎和II型混合性冷球蛋白血症患者的外周血淋巴细胞经商陆丝裂原刺激的细胞系中，已经描述了类似35G6的细胞。这些观察结果得到了证实，此外，还表明这些培养物中的大多数WAXID阳性细胞对17.109和G6XId是阴性的。在没有免疫球蛋白反应性的情况下，WAXID的存在表明WAXID与一种抗原特异性而不是与免疫球蛋白有更直接的关联，它与RF活性的关联可能是偶然的。推测这些WAXID阳性的RF阴性抗体可能作为一种普遍存在的病原体的天然抗体发挥生理学作用，而免疫球蛋白的反应性是伴随着WAXID阳性的RF阴性细胞的增殖而导致的体细胞多样化的结果。
The WA cross-idiotype (XId) is the major XId among human monoclonal rheumatoid factors (mRF) and is almost always associated with the light (L) chain XId, 17.109, and the heavy (H) chain XId, G6. A cell line, 35G6, was cloned that bears the WA XId, but shows no reactivity with immunoglobulin G (IgG) and is negative for the 17.109 and G6 XIds. The 35G6 L chain appears to be derived from the same VKIII-JKI genes as most WA mRFs L chains. In contrast to the WA mRFs H chains in which VH1 genes are used, the 35G6 IgM expresses a VH3 gene. Sequence comparisons with other WA XId-positive mRF suggested several common structural features that may be related to the WA XId and differences that may relate to lack of IgG reactivity. Cells similar to 35G6 have previously been described in pokeweed mitogen-stimulated cell lines of peripheral blood lymphocytes from normal individuals and patients with rheumatoid arthritis and type II mixed cryoglobulinemia. These observations were confirmed, and in addition, it was shown that the majority of WA XId-positive cells in these cultures were negative for the 17.109 and G6 XIds. The presence of the WA XId in the absence of IgG reactivity suggests that the WA XId is more directly associated with an antigen specificity other than IgG, and its association with RF activity may be incidental. It is postulated that these WA XId-positive RF-negative antibodies may serve a physiologic role as natural antibodies to a pervasive pathogen, and that IgG reactivity is a consequence of somatic diversification accompanying proliferation of the WA XId-positive RF-negative cell.