Souto-Carneiro M M, Burkhardt H, Müller E C, Hermann R, Otto A, Kraetsch H G, Sack U, König A, Heinegård D, Müller-Hermelink H K, Krenn V
Institute for Pathology, University of Wurzburg, Wurzburg, Germany.
J Immunol. 2001 Mar 15;166(6):4202-8. doi: 10.4049/jimmunol.166.6.4202.
Joint-specific self-Ags are considered to play an important role in the induction of synovial T and B cell expansion in human rheumatoid arthritis (RA). However, the nature of these autoantigens is still enigmatic. In this study a somatically mutated IgG2 lambda B cell hybridoma was established from the synovial membrane of an RA patient and analyzed for its Ag specificity. A heptameric peptide of cartilage oligomeric matrix protein (COMP) could be characterized as the target structure recognized by the human synovial B cell hybridoma. The clonotypic V(H) sequences of the COMP-specific hybridoma could also be detected in synovectomy material derived from five different RA patients but in none of the investigated osteoarthritis cases (n = 5), indicating a preferential usage of V(H) genes closely related to those coding for a COMP-specific Ag receptor in RA synovial B cells. Moreover, the COMP heptamer was preferentially recognized by circulating IgG in RA (n = 22) compared with osteoarthritis patients (n = 24) or age-matched healthy controls (n = 20; both p < 0.0001). Hence, the COMP-specific serum IgG is likely to reflect local immune responses toward a cartilage- and tendon-restricted Ag that might be crucial to the induction of tissue damage in RA.
关节特异性自身抗原被认为在人类类风湿关节炎（RA）滑膜T和B细胞扩增的诱导过程中发挥重要作用。然而，这些自身抗原的性质仍然是个谜。在本研究中，从一名RA患者的滑膜中建立了一株经体细胞突变的IgG2λ B细胞杂交瘤，并分析了其抗原特异性。软骨寡聚基质蛋白（COMP）的七聚体肽可被鉴定为人类滑膜B细胞杂交瘤识别的靶结构。在来自五名不同RA患者的滑膜切除材料中也能检测到COMP特异性杂交瘤的克隆型V(H)序列，但在所研究的骨关节炎病例（n = 5）中均未检测到，这表明RA滑膜B细胞中优先使用与编码COMP特异性抗原受体的基因密切相关的V(H)基因。此外，与骨关节炎患者（n = 24）或年龄匹配的健康对照（n = 20；两者p < 0.0001）相比，RA患者（n = 22）循环IgG对COMP七聚体的识别更为优先。因此，COMP特异性血清IgG可能反映了针对软骨和肌腱限制性抗原的局部免疫反应，这可能对RA中组织损伤的诱导至关重要。
