Mihaesco E, Ayadi H, Congy N, Gendron M C, Roy J P, Heyermann H, Frangione B, Brouet J C
Laboratory of Immunochemistry and Immunopathology, Institut National de la Santé et de la Recherche Médicale U 108, Hôpital Saint-Louis, Paris, France.
J Biol Chem. 1989 Dec 25;264(36):21481-5.
Human monoclonal IgM having an antibody activity directed to myelin-associated glycoprotein have distinctive features. Amino-terminal sequence of light and heavy chains from 6 IgM kappa that we have previously studied indicated that heavy chains belong to the VHIII subgroup, whereas light chains belong to 3 different subgroups of variability (V kappa I 2, V kappa II 1, and V kappa IV 3). We report here the complete sequence of the variable domain of 3 L chains: 2 V kappa IV and 1 V kappa II subgroups. Strikingly an unusually high degree of mutations clustered in the complementarity-determining regions (CDR) 1 and CDR 3 was found and the variable regions were joined to three different JK segments. Amino acid substitutions did not yield similar sequence in the CDRs suggesting that the kappa chains had no predominant role in the unique binding activity of these IgM or alternatively they are directed against different epitopes. Data are consistent with the previously reported lack of easily demonstrated public idiotopes common to anti-myelin-associated glycoprotein IgM. The pathogenesis of these IgM autoantibodies is most likely different from that of previously studied monoclonal rheumatoid factors or cold agglutinins where a genetic restriction of L or H chains or both has been observed.
具有针对髓鞘相关糖蛋白抗体活性的人单克隆IgM具有独特特征。我们之前研究的6种IgM κ轻链和重链的氨基末端序列表明，重链属于VHIII亚组，而轻链属于3个不同的可变亚组（VκI 2、VκII 1和VκIV 3）。我们在此报告3条轻链可变区的完整序列：2条VκIV和1条VκII亚组。令人惊讶的是，在互补决定区（CDR）1和CDR 3中发现了异常高程度的突变聚集，并且可变区与三个不同的JK片段相连。氨基酸替换在CDR中未产生相似序列，这表明κ链在这些IgM的独特结合活性中没有主要作用，或者它们针对不同的表位。数据与先前报道的抗髓鞘相关糖蛋白IgM缺乏易于证明的公共独特型一致。这些IgM自身抗体的发病机制很可能与先前研究的单克隆类风湿因子或冷凝集素不同，在后者中已观察到轻链或重链或两者的基因限制。
