Chen P P, Fong S, Carson D A
Department of Basic and Clinical Research, Research Institute of Scripps, La Jolla, California.
Rheum Dis Clin North Am. 1987 Dec;13(3):545-68.
Many human RF-associated crossreactive idiotypes (CRIs) have been defined. Since these CRIs probably are the phenotypic markers of Ig variable region genes, the data suggest that human RFs employ several Ig variable region genes which are common among outbred human populations. There are at least four types of stimuli which can trigger RF production. They are aggregated IgG in the form of antigen-antibody complexes, exogenous antigens bearing cross-reactive determinants to human IgG, autologous antibodies which mimic the Fc region of human IgG, and polyclonal B cell activators. Transient RF secretion is regularly induced by antigen-antibody complexes during secondary immune responses. In normal human subjects, RFs may be produced primarily by the B cells which bind mouse red cells, or express Leu l markers on their surface. Leu l is the human homolog of Ly l in mice. Upon polyclonal stimulation, these Ly l B cells secrete IgM autoantibodies. Combined protein and DNA sequencing studies reveal that human RFs utilize a small number of light chain variable region genes, together with several heavy chain variable regions genes. In contrast, by mRNA sequencing, murine RFs were found to employ many heavy and light chain variable region genes which belong to various gene families. Two human RF-related light chain variable region genes have been cloned and characterized. One germ-line Vk gene (designated Humkv325) is identical to four RF light chain sequences from unrelated individuals, and differs from the other eight RF light chains by one to seven amino acid residues. These results demonstrate that this RF-related Vk gene is both widely distributed and conserved among outbred human populations.
许多与人类类风湿因子（RF）相关的交叉反应性独特型（CRI）已被定义。由于这些CRI可能是Ig可变区基因的表型标记，数据表明人类RF利用了几种在远交人群中常见的Ig可变区基因。至少有四种类型的刺激可以触发RF的产生。它们是以抗原 - 抗体复合物形式存在的聚集IgG、带有与人IgG交叉反应决定簇的外源性抗原、模拟人IgG Fc区的自身抗体以及多克隆B细胞激活剂。在二次免疫反应期间，抗原 - 抗体复合物会定期诱导短暂的RF分泌。在正常人类受试者中，RF可能主要由结合小鼠红细胞或其表面表达Leu 1标记的B细胞产生。Leu 1是小鼠Ly 1的人类同源物。在多克隆刺激下，这些Ly 1 B细胞分泌IgM自身抗体。蛋白质和DNA测序联合研究表明，人类RF利用少量轻链可变区基因以及几种重链可变区基因。相比之下，通过mRNA测序发现，小鼠RF使用许多属于不同基因家族的重链和轻链可变区基因。两个与人类RF相关的轻链可变区基因已被克隆和鉴定。一个种系Vk基因（命名为Humkv325）与来自无关个体的四个RF轻链序列相同，与其他八个RF轻链在一至七个氨基酸残基上存在差异。这些结果表明，这个与RF相关的Vk基因在远交人群中广泛分布且保守。
