Solomon A, Weiss D T, Murphy C, Fu S M, Robbins D L
Department of Medicine, University of Tennessee Medical Center/Graduate School of Medicine, Knoxville 37920.
J Immunol. 1994 Aug 15;153(4):1658-64.
The primary structural features and serologic properties of a newly recognized human lambda light (L) chain V region subgroup (V lambda VIII) were elucidated through study of two monoclonal L chains, Bence Jones proteins HAG and BIV. The V region amino acid sequences of these components were highly homologous to each other and to that deduced from the prototypic V lambda VIII cDNA, Humla8f10, which encodes the L chains of the IgM lambda rheumatoid factor HAF10. Proteins HAG and BIV could be classified as members of the V lambda VIII subgroup and distinguished from L chains of the V lambda I, V lambda II, V lambda III, V lambda IV, and V lambda VI subgroups on the basis of amino acid sequence. In addition to distinctive residues found within the V lambda gene-encoded portion of the molecules, L chains HAG, BIV, and HAF10 contained remarkably different second complementarity-determining regions (CDR2) that consisted of 11 residues, rather than the seven typically found among members of the other five V lambda subgroups. This elongated structure would presumably impart to the ligand-binding site of lambda VIII molecules a markedly different canonical structure compared with those of lambda I, lambda II, lambda III, lambda IV, and lambda VI L chains. By using Bence Jones protein HAG as an immunogen, we obtained polyclonal and monoclonal anti-V lambda VIII subgroup-specific Abs that were used to identify and quantify lambda VIII-related molecules in normal and pathologic states. Among the Ig lambda components present in the serum of normal individuals, approximately 3% had lambda VIII L chains, a frequency comparable to that found among monoclonal Ig lambda proteins or surface(s) Ig lambda+ cells obtained from patients with malignant plasma cell- or B cell-related disorders, respectively. In contrast, lambda VIII L chains were detected on approximately 19% of monoclonal IgM lambda rheumatoid factors produced by B cell lines established from PBLs or synovial cells from patients with rheumatoid arthritis. The results of our studies provide new information on the structural and immunochemical features of lambda VIII L chains and the possible functional importance of the human V lambda VIII subgroup.
通过对两种单克隆轻链（Bence Jones蛋白HAG和BIV）的研究，阐明了一种新识别的人λ轻链（L）链V区亚组（VλVIII）的主要结构特征和血清学特性。这些成分的V区氨基酸序列彼此高度同源，也与从原型VλVIII cDNA（Humla8f10）推导的序列高度同源，该cDNA编码IgMλ类风湿因子HAF10的轻链。蛋白HAG和BIV可归类为VλVIII亚组的成员，并根据氨基酸序列与VλI、VλII、VλIII、VλIV和VλVI亚组的轻链区分开来。除了在分子的Vλ基因编码部分发现的独特残基外，轻链HAG、BIV和HAF10还含有明显不同的第二个互补决定区（CDR2），其由11个残基组成，而不是在其他五个Vλ亚组成员中通常发现的7个残基。与VλI、VλII、VλIII、VλIV和VλVI轻链相比，这种延长的结构可能会赋予VλVIII分子的配体结合位点明显不同的典型结构。通过使用Bence Jones蛋白HAG作为免疫原，我们获得了多克隆和单克隆抗VλVIII亚组特异性抗体，用于识别和定量正常和病理状态下与VλVIII相关的分子。在正常个体血清中存在的Igλ成分中，约3%具有VλVIII轻链，这一频率与分别从恶性浆细胞或B细胞相关疾病患者获得的单克隆Igλ蛋白或表面Igλ+细胞中的频率相当。相比之下，在从类风湿性关节炎患者的外周血淋巴细胞（PBL）或滑膜细胞建立的B细胞系产生的约19%的单克隆IgMλ类风湿因子上检测到VλVIII轻链。我们的研究结果提供了关于VλVIII轻链的结构和免疫化学特征以及人VλVIII亚组可能的功能重要性的新信息。
