Chapman C J, Spellerberg M B, Smith G A, Carter S J, Hamblin T J, Stevenson F K
Tenovus Laboratory, Southampton University Hospitals, UK.
J Immunol. 1993 Jul 15;151(2):1051-61.
A significant proportion of patients with B cell tumors secrete IgM mAb that recognize a carbohydrate autoantigen (li) on the red cell surface. The majority bear an idiotope (Id) that arises from heavy chains encoded by the VH4-21 gene segment, indicating unusual restriction of autoantibody specificity to a single VH gene. Polyclonal anti-li antibodies are also synthesized transiently by normal B cells following certain infections, and we have analyzed the role of the VH4-21 gene in encoding these antibodies. Levels of Id in sera of patients following infection with EBV or Mycoplasma pneumoniae were significantly raised (p < 0.01), and the Id-positive Ig reacted with patients' red cells. Id-positive B cell clones were established from four EBV-infected patients, and 6/6 of the IgM-Id agglutinated red cells. Nucleotide sequence analysis revealed involvement of the VH4-21 gene in all cases, with remarkably little change from the germ-line sequence. However, D segments were heterogeneous, and light chains differed. These results indicate that the same VH gene is used both by polyclonal autoantibodies produced in response to infection, and by B cell tumors. However, the lack of mutations would not appear to give an opportunity for Ag selection to drive affinity maturation of these autoantibodies.
相当一部分B细胞肿瘤患者分泌识别红细胞表面碳水化合物自身抗原（li）的IgM单克隆抗体。大多数抗体带有由VH4-21基因片段编码的重链产生的独特型（Id），这表明自身抗体特异性异常地局限于单个VH基因。正常B细胞在某些感染后也会短暂合成多克隆抗li抗体，我们分析了VH4-21基因在编码这些抗体中的作用。感染EB病毒或肺炎支原体的患者血清中Id水平显著升高（p < 0.01），且Id阳性Ig与患者红细胞发生反应。从4名EB病毒感染患者中建立了Id阳性B细胞克隆，其中6/6的IgM-Id使红细胞凝集。核苷酸序列分析显示所有病例均涉及VH4-21基因，与种系序列相比变化极小。然而，D片段是异质的，轻链也不同。这些结果表明，感染后产生的多克隆自身抗体和B细胞肿瘤都使用相同的VH基因。然而，缺乏突变似乎没有为抗原选择驱动这些自身抗体的亲和力成熟提供机会。
