Morbach Henner, Wiegering Verena, Richl Petra, Schwarz Tobias, Suffa Nadine, Eichhorn Eva-Maria, Eyrich Matthias, Girschick Hermann J
Vivantes Children's Hospital, Berlin-Friedrichshain, Germany): Children's Hospital and University of Würzburg, Würzburg, Germany.
Arthritis Rheum. 2011 Nov;63(11):3458-66. doi: 10.1002/art.30569.
B cells impact the perpetuation of chronic inflammatory or autoimmune diseases in multiple ways. A role of B cells as antigen-presenting cells (APCs) in the pathogenesis of chronic arthritis in humans has been suggested; however, as of yet the presence of such B cells at the site of inflammation has not been demonstrated. This study was undertaken to investigate whether synovial B cells in patients with juvenile idiopathic arthritis (JIA) might display features of APCs.
The frequency, phenotype, and immunoglobulin repertoire of synovial B cells were studied by flow cytometry and single-cell polymerase chain reaction (PCR). Cytokine expression by B cells was analyzed by real-time PCR, and interaction between B cells and T cells was investigated in a mixed lymphocyte culture.
CD27+IgD- and CD27-IgD- B cells accumulated in the joints of JIA patients and displayed an activated phenotype. Both B cell subsets expressed hypermutated and class-switched immunoglobulins, indicators of memory B cells. The accumulating memory B cells expressed the costimulatory molecules CD80/CD86 and showed a higher capacity to activate allogeneic T cells and prime a Th1 phenotype than their peripheral blood counterparts.
Activated immunoglobulin class-switched CD27- and CD27+ memory B cells, indicating a phenotype of APCs with expression of costimulatory molecules, accumulate in the joints of patients with JIA and might be involved in the amplification of pathogenic T cell activation. These findings provide evidence that B cells play an antibody-independent immunopathologic role in human chronic inflammatory arthritis of childhood.
B细胞以多种方式影响慢性炎症或自身免疫性疾病的持续存在。已有研究提示B细胞作为抗原呈递细胞(APC)在人类慢性关节炎发病机制中发挥作用;然而,目前尚未证实此类B细胞在炎症部位的存在。本研究旨在探讨幼年特发性关节炎(JIA)患者的滑膜B细胞是否可能表现出APC的特征。
通过流式细胞术和单细胞聚合酶链反应(PCR)研究滑膜B细胞的频率、表型和免疫球蛋白库。通过实时PCR分析B细胞的细胞因子表达,并在混合淋巴细胞培养中研究B细胞与T细胞之间的相互作用。
CD27+IgD-和CD27-IgD- B细胞在JIA患者关节中积聚,并表现出活化表型。两个B细胞亚群均表达高度突变和类别转换的免疫球蛋白,这是记忆B细胞的指标。积聚的记忆B细胞表达共刺激分子CD80/CD86,与外周血中的同类细胞相比,其激活同种异体T细胞并引发Th1表型的能力更高。
活化的免疫球蛋白类别转换的CD27-和CD27+记忆B细胞,表明具有共刺激分子表达的APC表型,在JIA患者关节中积聚,并可能参与致病性T细胞激活的放大。这些发现提供了证据,表明B细胞在儿童慢性炎症性关节炎中发挥非抗体依赖性免疫病理作用。