非典型B细胞(atBC)是不同的B细胞群,并且代表健康成人个体的外周血(PB)中的约5%的B细胞。然而,在成人中,这些细胞在慢性感染的条件下扩增,炎症,原发性免疫缺陷,自身免疫性疾病,和衰老。它们的免疫表型的特征在于缺乏CD21表达和人类记忆B细胞标记CD27。在这项研究中,我们调查了不同儿科病理条件下atBC的免疫表型,并将其扩增与儿童的临床诊断相关联。我们能够回顾性评估1,571个连续的PB样本,对应于1,180名儿科患者,通过使用9色流式细胞仪面板。结果,与儿科健康队列相比,证实了患者样品中atBC的扩增,占总B细胞的百分比大于5%。区分了四个IgM和IgD表达不同的亚群:IgMIgD,仅IgM+-,仅限IgD+,和IgM-IgA-。IgG+atBC在IgM-IgD-亚群中占优势。此外,这项研究强调了ATBC的一些特征,例如低CD38表达,CD24的异质性,CD19的高表达和大细胞大小。我们还证明,儿科队列中atBC的增加与免疫缺陷相关,自身免疫,炎症,和血液病,与以前主要在成人中进行的研究一致。此外,我们的流式细胞术聚类分析证实了atBC替代B起源的最新假设。
Atypical B cells (atBCs) are a distinct B-cell population and represent approximately 5% of B cells in peripheral blood (PB) of healthy adult individuals. However, in adults these cells are expanded in conditions of chronic infections, inflammation, primary
immunodeficiencies, autoimmune diseases, and aging. Their immunophenotype is characterized by the lack of CD21 expression and the hallmark human memory B-cell marker CD27. In this
study, we investigated the immunophenotype of atBCs in different pediatric pathological conditions and correlated their expansion with the children\'s clinical diagnosis. We were able to retrospectively evaluate 1,571 consecutive PB samples, corresponding to 1,180 pediatric patients, by using a 9-color flow-cytometric panel. The results, compared with a pediatric healthy cohort, confirmed an expansion of atBCs in patient samples with percentages greater than 5% of total B cells. Four subpopulations with different expressions of IgM and IgD were discriminated: IgM+IgD+, IgM+-only, IgD+-only, and IgM-IgD-. IgG+ atBCs were predominant in the IgM- IgD- subpopulation. Moreover, the
study highlighted some features of atBCs, such as a low CD38 expression, a heterogeneity of CD24, a high expression of CD19 and a large cell size. We also demonstrated that an increase of atBCs in a pediatric cohort is correlated with
immunodeficiencies, autoimmune, inflammatory, and hematological disorders, consistent with previous studies mainly performed in adults. Furthermore, our flow cytometric clustering analysis corroborated the recent hypothesis of an alternative B origin for atBCs.