Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia.
Unidad de Citometría, Facultad de Medicina, Sede de Investigación Universitaria, Universidad de Antioquia UdeA, Medellín, Colombia.
Clin Exp Immunol. 2021 May;204(2):221-238. doi: 10.1111/cei.13576. Epub 2021 Mar 2.
Patients with rheumatoid arthritis (RA) may be classified as seropositive or seronegative according to the presence of autoantibodies. An abnormal B cell phenotype and function could be one of the main components of the immunopathology of seropositive patients; however, there is little information regarding B cell defects in these patients. This study shows a broad characterization of the B cell phenotype and function in patients with seropositive RA. We focused mainly on the evaluation of subsets, the expression of modulatory molecules of cell activation (CD22, FcɣRIIb and FcµR), calcium mobilization, global tyrosine phosphorylation, expression of activation markers, cytokine and immunoglobulin (Ig) production, proliferation and the in-vitro generation of plasma cells. Increased frequency of CD27 IgM IgD and CD21 B cells was observed in patients with seropositive RA compared with healthy donors (HD). Decreased expression of CD22 was primarily found in memory B cells of patients with RA regardless of seropositivity. B cells from seropositive patients exhibited normal proliferation, calcium mobilization kinetics and global tyrosine phosphorylation, but showed an increased frequency of CD86 B cells compared with HD. B cells of seropositive patients secrete less interleukin-10 after in-vitro activation and showed a decreased frequency of plasma cell differentiation and IgM production compared with HD. Our data indicate that patients with seropositive RA have an increased frequency of atypical B cell populations previously associated with chronic activation and antigen exposure. This may result in the observed low responsiveness of these cells in vitro.
患有类风湿关节炎（RA）的患者可根据自身是否存在自身抗体而被分为血清阳性或血清阴性。异常的 B 细胞表型和功能可能是血清阳性患者免疫病理学的主要组成部分之一；然而，关于这些患者的 B 细胞缺陷，我们知之甚少。本研究对血清阳性 RA 患者的 B 细胞表型和功能进行了广泛的特征描述。我们主要集中于评估亚群、细胞激活调节分子（CD22、FcγRIIb 和 FcμR）、钙动员、整体酪氨酸磷酸化、激活标志物表达、细胞因子和免疫球蛋白（Ig）产生、增殖以及体外浆细胞生成的情况。与健康供体（HD）相比，血清阳性 RA 患者的 CD27 IgM IgD 和 CD21 B 细胞的频率增加。RA 患者的记忆 B 细胞中主要发现 CD22 表达降低，而与血清阳性无关。与 HD 相比，血清阳性患者的 B 细胞表现出正常的增殖、钙动员动力学和整体酪氨酸磷酸化，但 CD86 B 细胞的频率增加。与 HD 相比，血清阳性患者的 B 细胞在体外激活后分泌的白细胞介素-10 减少，并且浆细胞分化和 IgM 产生的频率降低。我们的数据表明，血清阳性 RA 患者存在先前与慢性激活和抗原暴露相关的异常 B 细胞群体频率增加。这可能导致这些细胞在体外的反应性降低。
