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单克隆抗轻链独特型作为人肿瘤性B淋巴细胞的肿瘤特异性探针。

Monoclonal anti-light chain idiotype as a tumor-specific probe for human neoplastic B lymphocytes.

作者信息

Wrightham M, Tutt A L, Glennie M J, Hamblin T J, Stevenson G T, Stevenson F K

出版信息

Blood. 1987 Mar;69(3):919-23.

PMID:2434161
Abstract

Tumor cells from patients with B cell neoplasms often secrete small amounts of free monoclonal light chains that can be found in the urine. Such tumor-derived light chains of the lambda type from a patient with typical chronic lymphocytic leukemia have been used to raise mouse monoclonal antibodies (MoAbs). A hybridoma-secreting antibody that recognized the idiotypic lambda chain but not normal lambda chains by a preliminary screen but which also reacted with idiotypic IgM from the patient's tumor cells was selected. This MoAb in fact recognized 1 in 20 X 10(3) molecules of pooled normal lambda chains, thus establishing its specificity for a private idiotypic determinant. It failed to give a detectable reaction with normal IgM, normal serum, or a panel of IgM paraproteins. The antibody bound to the patient's neoplastic B cells but not to normal tonsillar cells. The site of binding of the antibody to idiotypic IgM is clearly separate from that of another MoAb specific for idiotypic determinants on heavy plus light chains, since the two showed additive binding curves. The determinant also appeared to be less available in dimeric lambda chains than in monomeric lambda chains or in idiotypic IgM. Antibodies to idiotypic determinants on light chains show some technical advantages and should be useful for monitoring and possibly treating B cell tumors, either alone or together with the more conventional anti-idiotypic antibodies that usually recognize the heavy and light chain combination.

摘要

B细胞肿瘤患者的肿瘤细胞常常分泌少量可在尿液中检测到的游离单克隆轻链。来自一名典型慢性淋巴细胞白血病患者的此类肿瘤衍生的λ型轻链已被用于制备小鼠单克隆抗体(MoAb)。通过初步筛选,选择了一种分泌抗体的杂交瘤,该抗体识别独特型λ链,但不识别正常λ链,且还与患者肿瘤细胞的独特型IgM发生反应。事实上,这种单克隆抗体能识别20×10³个混合正常λ链分子中的1个,从而确定了其对一个独特的独特型决定簇的特异性。它与正常IgM、正常血清或一组IgM副蛋白均未产生可检测到的反应。该抗体与患者的肿瘤性B细胞结合,但不与正常扁桃体细胞结合。该抗体与独特型IgM的结合位点明显不同于另一种对重链加轻链上独特型决定簇具有特异性的单克隆抗体的结合位点,因为两者呈现加和性结合曲线。该决定簇在二聚体λ链中的可及性似乎比在单体λ链或独特型IgM中的要低。针对轻链上独特型决定簇的抗体具有一些技术优势,单独或与通常识别重链和轻链组合的更传统的抗独特型抗体一起,应该对监测和可能治疗B细胞肿瘤有用。

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