Jefferies L C, Silverman G J, Carchidi C M, Silberstein L E
Hospital of the University of Pennsylvania, Department of Pathology and Laboratory Medicine, Philadelphia 19104.
Clin Immunol Immunopathol. 1992 Nov;65(2):119-28. doi: 10.1016/0090-1229(92)90214-9.
VKIII light (L) chains are commonly expressed by human autoantibodies with diverse binding specificities, including red blood cell antigens. To better understand the physiologic and pathologic expression of these L chain variable region genes, we have created a panel of murine monoclonal anti-idiotypic antibodies by immunization with a human lymphoblastoid B cell line that secretes an IgM VKIII autoantibody specific for the I red blood cell carbohydrate determinant. The binding specificities of these nine murine monoclonal antibodies, termed IV.1-IV.9, were evaluated against a large panel of monoclonal Ig proteins and compared to two previously well-characterized monoclonal anti-idiotypes, 6B6.6 and 17.109; these two anti-idiotypes have been shown to primarily identify VKIII rheumatoid factors derived from the kv328 (VKIIIa) and kv325 (VKIIIb) genes, respectively. In contrast, our anti-idiotypic antibodies identified (public) cross-reactive idiotypes present on many VKIII proteins that included both anti-erythrocyte and rheumatoid factor autoantibodies. Certain anti-idiotypic antibodies (IV.2 and IV.6) were restricted to VKIIIa L chains but differed from the 6B6.6 anti-idiotype by binding to a larger subset of VKIIIa proteins representing the products of at least two VKIIIa genes. One antibody of our panel (IV.5) recognized a private idiotope expressed only by the immunizing antibody. Using the panel of anti-idiotypic antibodies to evaluate erythrocyte autoantibodies with different serologic specificities, we found striking heterogeneity of L chain idiotype expression, even among known VKIII anti-i/I autoantibodies. These findings differ from the recently described structural and idiotypic conservation associated with the H chain of anti-i/I autoantibodies. From correlations of idiotypic reactivity with L chains of known sequence, it is postulated that the observed heterogeneity of L chain idiotype expression is due to differences in the genetic origin and/or somatic diversification of L chain variable region genes. Furthermore, subtle variability of L chain structure may contribute in part to the differences in fine binding specificity among anti-I and anti-i autoantibodies.
VKIII轻链通常由具有多种结合特异性的人类自身抗体表达，包括红细胞抗原。为了更好地理解这些轻链可变区基因的生理和病理表达，我们通过用一种人类淋巴母细胞B细胞系免疫创建了一组鼠单克隆抗独特型抗体，该细胞系分泌一种针对I型红细胞碳水化合物决定簇的IgM VKIII自身抗体。针对一大组单克隆Ig蛋白评估了这九种称为IV.1-IV.9的鼠单克隆抗体的结合特异性，并与两种先前已充分表征的单克隆抗独特型抗体6B6.6和17.109进行了比较；这两种抗独特型抗体已被证明分别主要识别源自kv328（VKIIIa）和kv325（VKIIIb）基因的VKIII类风湿因子。相比之下，我们的抗独特型抗体识别出许多VKIII蛋白上存在的（公共）交叉反应独特型，这些蛋白包括抗红细胞和类风湿因子自身抗体。某些抗独特型抗体（IV.2和IV.6）仅限于VKIIIa轻链，但与6B6.6抗独特型不同，它们能结合更大的代表至少两个VKIIIa基因产物的VKIIIa蛋白子集。我们组中的一种抗体（IV.5）识别仅由免疫抗体表达的个体独特型。使用抗独特型抗体组评估具有不同血清学特异性的红细胞自身抗体，我们发现轻链独特型表达存在显著异质性，即使在已知的VKIII抗-i/I自身抗体中也是如此。这些发现与最近描述的抗-i/I自身抗体重链相关的结构和独特型保守性不同。从独特型反应性与已知序列轻链的相关性推测出，观察到的轻链独特型表达异质性是由于轻链可变区基因的遗传起源和/或体细胞多样化的差异。此外，轻链结构的细微变化可能部分导致抗-I和抗-i自身抗体之间精细结合特异性的差异。
