Knight G B, Agnello V, Bonagura V, Barnes J L, Panka D J, Zhang Q X
Department of Laboratory Medicine, Lahey Clinic, Burlington, Massachusetts 01805.
J Exp Med. 1993 Dec 1;178(6):1903-11. doi: 10.1084/jem.178.6.1903.
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.
WA交叉独特型（XId）是人类单克隆类风湿因子（mRF）中的主要XId，几乎总是与轻链（L）XId 17.109和重链（H）XId G6相关。克隆了一个细胞系35G6，它带有WA XId，但与免疫球蛋白G（IgG）无反应性，且17.109和G6 XIds呈阴性。35G6轻链似乎与大多数WA mRFs轻链源自相同的VKIII-JKI基因。与使用VH1基因的WA mRFs重链不同，35G6 IgM表达VH3基因。与其他WA XId阳性mRF的序列比较表明了几个可能与WA XId相关的共同结构特征以及可能与缺乏IgG反应性相关的差异。在来自正常个体、类风湿性关节炎患者和II型混合性冷球蛋白血症患者的外周血淋巴细胞的商陆有丝分裂原刺激细胞系中，先前已描述过类似于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大多数WA XId阳性细胞的17.109和G6 XIds呈阴性。在缺乏IgG反应性的情况下存在WA XId表明，WA XId与除IgG以外的抗原特异性更直接相关，其与RF活性的关联可能是偶然的。据推测，这些WA XId阳性RF阴性抗体可能作为针对普遍存在病原体的天然抗体发挥生理作用，并且IgG反应性是WA XId阳性RF阴性细胞增殖伴随的体细胞多样化的结果。
