Department of Clinical Immunology and Allergology, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
J Immunol. 2010 Dec 1;185(11):6431-8. doi: 10.4049/jimmunol.0903876. Epub 2010 Nov 1.
Increased proportions of naive B cell subset and B cells defined as CD27(neg)CD21(neg)CD38(neg) are frequently found in patients with common variable immunodeficiency (CVID) syndrome. Current methods of polychromatic flow cytometry and PCR-based detection of κ deletion excision circles allow for fine definitions and replication history mapping of infrequent B cell subsets. We have analyzed B cells from 48 patients with CVID and 49 healthy controls to examine phenotype, frequency, and proliferation history of naive B cell subsets. Consistent with previous studies, we have described two groups of patients with normal (CVID-21norm) or increased (CVID-21lo) proportions of CD27(neg)CD21(neg)CD38(neg) B cells. Upon further analyses, we found two discrete subpopulations of this subset based on the expression of CD24. The B cell subsets showed a markedly increased proliferation in CVID-21lo patients as compared with healthy controls, suggesting developmental arrest rather than increased bone marrow output. Furthermore, when we analyzed CD21(pos) naive B cells, we found two different subpopulations based on IgM and CD24 expression. They correspond to follicular (FO) I and FO II cells previously described in mice. FO I subset is significantly underrepresented in CVID-21lo patients. A comparison of the replication history of naive B cell subsets in CVID patients and healthy controls implies refined naive B cell developmental scheme, in which human transitional B cells develop into FO II and FO I. We propose that the CD27(neg)CD21(neg)CD38(neg) B cells increased in some of the CVID patients originate from the two FO subsets after loss of CD21 expression.
在普通变异型免疫缺陷（CVID）综合征患者中，经常发现幼稚 B 细胞亚群和被定义为 CD27（neg）CD21（neg）CD38（neg）的 B 细胞比例增加。多色流式细胞术和基于 PCR 的 κ 缺失切除环检测的当前方法允许对罕见 B 细胞亚群进行精细定义和复制历史映射。我们分析了 48 例 CVID 患者和 49 例健康对照者的 B 细胞，以检查幼稚 B 细胞亚群的表型、频率和增殖历史。与先前的研究一致，我们描述了两组患者，一组患者具有正常（CVID-21norm）或增加（CVID-21lo）比例的 CD27（neg）CD21（neg）CD38（neg）B 细胞。进一步分析发现，根据 CD24 的表达，该亚群有两个离散的亚群。与健康对照者相比，CVID-21lo 患者的 B 细胞亚群增殖明显增加，表明发育停滞而不是骨髓输出增加。此外，当我们分析 CD21（pos）幼稚 B 细胞时，我们根据 IgM 和 CD24 的表达发现了两个不同的亚群。它们与先前在小鼠中描述的滤泡（FO）I 和 FO II 细胞相对应。FO I 亚群在 CVID-21lo 患者中明显代表性不足。对 CVID 患者和健康对照者幼稚 B 细胞亚群复制历史的比较表明，幼稚 B 细胞发育方案得到了细化，人类过渡性 B 细胞发育为 FO II 和 FO I。我们提出，一些 CVID 患者中增加的 CD27（neg）CD21（neg）CD38（neg）B 细胞起源于丧失 CD21 表达后的两个 FO 亚群。
