Ermel R W, Kenny T P, Wong A, Solomon A, Chen P P, Robbins D L
University of California at Davis.
Arthritis Rheum. 1994 Jun;37(6):860-8. doi: 10.1002/art.1780370614.
To further our understanding about the molecular genetics of rheumatoid factor (RF) in rheumatoid arthritis (RA).
The heavy and light chain variable region (V) genes of 5 new human monoclonal IgM RFs were cloned and sequenced using the polymerase chain reaction and the dideoxynucleotide termination method.
The results reveal the recurrent usage in two RA patients of a novel V lambda 3 germline gene, designated Humlv3c93. Specifically, in 2 of 3 RFs (C93 and D53) from one patient, the light chains in the V lambda gene-encoded region were identical to each other and to the light chain of an RF (H4) from another patient. Serologically, the light chains of these 3 RFs were classified as members of the V lambda 3b sub-subgroup. Each of the RFs was encoded by a different VH gene. Both C93 and D53 bound specifically with human and rabbit IgG, whereas H4 was monospecific for rabbit IgG.
Since the lv3c93 gene is not homologous to any reported V lambda sequence from natural autoantibodies, it is possible that lv3c93 may represent a disease-specific RF-related V lambda gene. Moreover, the amino acid sequence CSGGSCY in the third complementarity-determining regions of 2 of the RF heavy chains is encoded by the DLR2 gene segment and has been found previously in 2 other RA-derived RFs, and thus may play a significant role in antigen binding.
进一步了解类风湿关节炎（RA）中类风湿因子（RF）的分子遗传学。
采用聚合酶链反应和双脱氧核苷酸末端终止法，克隆并测序了5种新的人单克隆IgM RF的重链和轻链可变区（V）基因。
结果显示，一种新的Vλ3种系基因Humlv3c93在两名RA患者中反复出现。具体而言，在一名患者的3种RF（C93和D53）中的2种中，Vλ基因编码区的轻链彼此相同，且与另一名患者的一种RF（H4）的轻链相同。血清学上，这3种RF的轻链被归类为Vλ3b亚亚组的成员。每种RF由不同的VH基因编码。C93和D53均与人及兔IgG特异性结合，而H4对兔IgG具有单特异性。
由于lv3c93基因与天然自身抗体中任何已报道的Vλ序列均不同源，因此lv3c93可能代表一种疾病特异性的RF相关Vλ基因。此外，2种RF重链的第三个互补决定区中的氨基酸序列CSGGSCY由DLR2基因片段编码，并且先前已在另外2种源自RA的RF中发现，因此可能在抗原结合中起重要作用。
