Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
J Immunol. 2012 Apr 1;188(7):3542-50. doi: 10.4049/jimmunol.1100577. Epub 2012 Feb 15.
Autoantibodies against citrullinated protein Ags (ACPA) are associated with the development of rheumatoid arthritis (RA). This immune response against citrullinated protein Ags, which is thought to be facilitated by certain MHC HLA-DR alleles, is highly specific for this disease and has been speculated to be involved in the pathogenesis. We have previously studied cultures of B cells for the production of Abs against HLA Ags. The aim of the current study was to examine the role of B cells in the production of ACPA in patients with RA. Peripheral blood B cells from RA patients and healthy people were cultured with EL4-B5, a murine cell line expressing human CD40L, and with T cell factors to stimulate the in vitro production of Abs by B cells isolated from peripheral blood. ACPA were produced by cultured B cells from RA patients, as determined by reactivity to cyclic citrullinated peptide (CCP). The results showed that 22% of the healthy persons tested also had B cells that could produce ACPA. Patients with HLA-DR alleles carrying the RA-associated shared epitope appeared to have more B cells with autoimmune potential for CCP than those without such HLA alleles (odds ratio 8.1, p = 0.001). In healthy individuals, anti-CCP-producing B cells were also observed more frequently if the RA-associated MHC genes were present (odds ratio 8.0, p = 0.01). Analysis of B cells in cultures may shed light on the interaction of genetic and environmental factors in the development of RA.
自身抗体针对瓜氨酸化蛋白抗原（ACPA）与类风湿关节炎（RA）的发展有关。这种针对瓜氨酸化蛋白抗原的免疫反应，被认为是由某些 MHC HLA-DR 等位基因介导的，对这种疾病具有高度特异性，并被推测与发病机制有关。我们之前研究了 B 细胞培养物中针对 HLA 抗原的 Abs 的产生。本研究的目的是研究 B 细胞在 RA 患者 ACPA 产生中的作用。用表达人 CD40L 的鼠细胞系 EL4-B5 与 T 细胞因子一起培养 RA 患者和健康人的外周血 B 细胞，以刺激从外周血分离的 B 细胞体外产生 Abs。通过对环瓜氨酸肽（CCP）的反应性，确定 RA 患者培养的 B 细胞产生了 ACPA。结果表明，在接受测试的健康人中，有 22%的人也有能够产生 ACPA 的 B 细胞。与没有这些 HLA 等位基因的患者相比，携带 RA 相关共享表位的 HLA-DR 等位基因的患者似乎具有更多具有 CCP 自身免疫潜能的 B 细胞（比值比 8.1，p=0.001）。在健康个体中，如果存在与 RA 相关的 MHC 基因，也会更频繁地观察到产生抗 CCP 的 B 细胞（比值比 8.0，p=0.01）。对培养物中的 B 细胞进行分析可能会揭示遗传和环境因素在 RA 发展中的相互作用。
