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单核样 B 细胞:一个表现出滤泡外免疫球蛋白基因体细胞高频突变证据的神秘 B 细胞亚群。

Monocytoid B cells: an enigmatic B cell subset showing evidence of extrafollicular immunoglobulin gene somatic hypermutation.

机构信息

Department of Pathology, the Norwegian Radiumhospital, University of Oslo, Oslo, Norway.

出版信息

Scand J Immunol. 2012 May;75(5):500-9. doi: 10.1111/j.1365-3083.2012.02688.x.

DOI:10.1111/j.1365-3083.2012.02688.x
PMID:22486786
Abstract

Monocytoid B cells are IgM(+) , IgD(-/+) , CD27(-) B cells, localized in the perisinusoidal area of the lymph node. These cells are especially prominent in infections such as those caused by toxoplasma and HIV. The ontogeny of monocytoid B cells with respect to B cell maturation is incompletely known. We analysed clonal expansion, somatic hypermutation and expression of activation-induced cytidine deaminase (AID) in monocytoid B cells. Sequence analysis of the rearranged immunoglobulin heavy chain genes amplified from microdissected monocytoid B cell zones with a high proportion of proliferating cells reveals the presence of multiple clones with low-level ongoing mutations (mean frequency: 0.46 × 10(-2) per bp). Mutation analysis of these ongoing mutations reveals strand bias, a preference of transitions over transversions as well as the occurrence of small deletions, as observed for somatically mutated immunoglobulin genes in the human germinal centre. Proliferation, ongoing mutation as well as expression of AID, combined, is evidence that monocytoid B cells acquire the mutations in the extrafollicular perisinusoidal area of the lymph node and pleads against a postgerminal centre B cell origin.

摘要

单核样 B 细胞是 IgM(+)、IgD(-/+)、CD27(-)B 细胞,定位于淋巴结的窦周隙。这些细胞在弓形虫和 HIV 等感染中尤为突出。单核样 B 细胞在 B 细胞成熟方面的个体发生尚不完全清楚。我们分析了克隆扩增、体细胞高频突变和激活诱导胞苷脱氨酶 (AID)的表达在单核样 B 细胞中的作用。从高比例增殖细胞的微切割单核样 B 细胞区室中扩增的重链免疫球蛋白基因的序列分析揭示了多个克隆的存在,这些克隆具有低水平的持续突变(平均频率:每个碱基 0.46×10(-2))。对这些持续突变的突变分析显示出链偏好性,即转换相对于颠换的偏好性,以及小缺失的发生,这与人类生发中心中体细胞突变的免疫球蛋白基因观察到的情况一致。增殖、持续突变以及 AID 的表达结合在一起,证明了单核样 B 细胞在淋巴结的滤泡外窦周隙获得了突变,这表明它们不是生发中心后 B 细胞的起源。

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