Kipps T J
Department of Basic and Clinical Research, Scripps Clinic, La Jolla, CA 92037.
Nouv Rev Fr Hematol (1978). 1988;30(5-6):293-8.
Chronic lymphocytic leukemia (CLL) represents a malignancy of the CD5 B cell. Such CD5 B cells constitute a minor B cell subpopulation in normal adults that recently has been implicated as a source of IgM autoantibodies. NHL of follicular center cell origin, on the other hand, generally do not co-express CD5, and may be considered neoplasms of B cells from a lineage(s) or differentiation stage(s) distinct from that of the CD5 B cell. We examined antibody-expressing malignant B cells from patients with CLL for reactivity with each of several mouse monoclonal antibodies (mAb) specific for immunoglobulin (Ig) cross-reactive idiotypes (CRI) associated with human autoantibodies. Nearly 20% of all Ig-expressing CLL were recognized by a mAb specific for a rheumatoid factor (RF) heavy-chain associated CRI. Furthermore, approximately 20% of the kappa light chain expressing CLL reacted with 17.109, a mAb specific for a kappa-light-chain-associated CRI. In contrast, NHL that do not co-express the CD5 surface antigen apparently react with these anti-CRI mAbs at significantly lower frequencies. None of the forty CD5-negative NHL tested reacted with the mAb specific for the Ig heavy chain associated CRI. Moreover, only one of 30 kappa light chain expressing CD5-negative NHL tested reacted with 17.109. We examined the molecular basis for the high frequency expression of autoantibody-associated CRIs in CLL. Analyses of the Ig kappa light chain cDNA reveals remarkable conservation in the nucleic acid sequence of the kappa light chain variable region gene (Vk gene) expressed by 17.109-reactive leukemic cells from unrelated patients.(ABSTRACT TRUNCATED AT 250 WORDS)
慢性淋巴细胞白血病(CLL)是一种CD5 B细胞的恶性肿瘤。此类CD5 B细胞在正常成年人中构成一小部分B细胞亚群,最近被认为是IgM自身抗体的来源。另一方面,滤泡中心细胞起源的非霍奇金淋巴瘤(NHL)通常不共表达CD5,可被视为来自与CD5 B细胞不同谱系或分化阶段的B细胞肿瘤。我们检测了慢性淋巴细胞白血病患者表达抗体的恶性B细胞与几种针对与人自身抗体相关的免疫球蛋白(Ig)交叉反应独特型(CRI)的小鼠单克隆抗体(mAb)的反应性。所有表达Ig的慢性淋巴细胞白血病中近20%被一种针对类风湿因子(RF)重链相关CRI的单克隆抗体识别。此外,约20%表达κ轻链的慢性淋巴细胞白血病与17.109反应,17.109是一种针对κ轻链相关CRI的单克隆抗体。相比之下,不共表达CD5表面抗原的非霍奇金淋巴瘤与这些抗CRI单克隆抗体的反应频率明显较低。所检测的40例CD5阴性非霍奇金淋巴瘤中无一例与针对Ig重链相关CRI的单克隆抗体反应。此外,所检测的30例表达κ轻链的CD5阴性非霍奇金淋巴瘤中只有1例与17.109反应。我们研究了慢性淋巴细胞白血病中自身抗体相关CRI高频表达的分子基础。对Igκ轻链cDNA的分析显示,来自无关患者的17.109反应性白血病细胞表达的κ轻链可变区基因(Vk基因)的核酸序列具有显著保守性。(摘要截短于250字)