Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
Ann Rheum Dis. 2013 Jul;72(7):1259-63. doi: 10.1136/annrheumdis-2012-202893. Epub 2013 Apr 26.
To study the characteristics and phenotype of anticitrullinated protein antibody (ACPA)-specific B cells in peripheral blood of patients with rheumatoid arthritis (RA).
Peripheral blood B cells from ACPA-positive patients with RA were cultured with or without stimulating factors. Following culture, supernatants were assessed for the presence of ACPA-IgG and non-specific total IgG by ELISA.
Following stimulation, ACPA were detectable in up to 100% of culture wells. Of interest, ACPA were also produced spontaneously by unstimulated peripheral blood mononuclear cells. In both cases, the average ACPA titre per culture well correlated with ACPA serum titres. No ACPA production was detectable in B cell cultures from ACPA-negative patients with RA or healthy controls. Importantly, FACS-sorting experiments located spontaneous ACPA production to the CD20 negative B cell population corresponding to circulating plasmablasts/cells.
ACPA-specific peripheral blood B cells are not confined to the CD20 positive memory pool, as circulating plasmablasts/cells spontaneously producing ACPA are also readily detectable. The latter points to an ongoing B cell immune response against citrullinated proteins and contrasts conventional immune responses against, for example, vaccines, where antigen-specific plasmablasts appear in peripheral blood only shortly after vaccination. These circulating, ACPA-specific plasmablasts/cells might represent targets for novel therapeutic interventions.
研究类风湿关节炎（RA）患者外周血中抗瓜氨酸化蛋白抗体（ACPA）特异性 B 细胞的特征和表型。
用或不用刺激因子培养 ACPA 阳性 RA 患者的外周血 B 细胞。培养后，通过 ELISA 检测上清液中 ACPA-IgG 和非特异性总 IgG 的存在情况。
刺激后，培养孔中高达 100%可检测到 ACPA。有趣的是，未刺激的外周血单核细胞也自发产生 ACPA。在这两种情况下，每个培养孔的平均 ACPA 效价与 ACPA 血清效价相关。在 ACPA 阴性 RA 患者或健康对照者的 B 细胞培养中未检测到 ACPA 产生。重要的是，FACS 分选实验将自发产生 ACPA 的细胞定位到对应循环浆母细胞/细胞的 CD20 阴性 B 细胞群。
ACPA 特异性外周血 B 细胞不仅局限于 CD20 阳性记忆池，因为循环浆母细胞/细胞也可自发产生 ACPA。后者表明针对瓜氨酸化蛋白的持续 B 细胞免疫反应，与针对例如疫苗的传统免疫反应形成对比，后者仅在接种疫苗后不久在外周血中出现抗原特异性浆母细胞。这些循环的 ACPA 特异性浆母细胞/细胞可能成为新的治疗干预的靶点。
