New insights into heterogeneity of peritoneal B-1a cells.

New insights into heterogeneity of peritoneal B-1a cells.
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DOI:
10.1111/nyas.12791
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发表时间:
2015-12
影响因子:
5.2
通讯作者:
Morse HC 3rd
Morse HC 3rd
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang H;Lin JX;Li P;Skinner J;Leonard WJ;Morse HC 3rd

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腹膜B-1a细胞的特征在于其表达CD 5和富集生殖系编码的IgM B细胞受体(BCR)。早期的研究表明,纯化的B-1a细胞中VDJ序列的多样性阵列的表达为理解B-1a细胞库的异质性提供了分子基础。抗原驱动的阳性选择和B-1a特异性祖细胞的鉴定表明B-1a细胞的多种来源。引入新的标志物,如PD-L2、CD 25、CD 73和PC 1(浆细胞同种异体抗原1,也称为外核苷酸磷酸二酯酶/焦磷酸酶1(ENPP 1)),进一步有助于鉴定表型和功能不同的B-1a亚群。在由这些新标记物定义的许多B-1a亚群中,PC 1是独特的,因为它将B-1a细胞细分为具有不同功能的PC 1hi和PC 1 lo亚群,例如产生天然IgM和肠道伊加,对肺炎球菌抗原PPS-3的应答,分泌白细胞介素(IL)-10,以及支持T辅助细胞1(TH 1)分化。这些子集的RNA测序(RNA-seq)揭示了参与细胞运动和免疫细胞运输的基因的差异表达。我们将讨论这些新的见解的基础上的异质性的B-1a细胞库。
Peritoneal B-1a cells are characterized by their expression of CD5 and enrichment for germ line–encoded IgM B cell receptors (BCRs). Early studies showing expression of a diverse array of VDJ sequences among purified B-1a cells provided a molecular basis for understanding the heterogeneity of the B-1a cell repertoire. Antigen-driven positive selection and the identification of B-1a specific progenitors suggest multiple origins of B-1a cells. The introduction of new markers such as PD-L2, CD25, CD73, and PC1 (plasma cell alloantigen 1, also known as ectonucleotide phosphodiesterase/pyrophosphatase 1 (ENPP1)) further helped to identify phenotypically and functionally distinct B-1a subsets. Among many B-1a subsets defined by these new markers, PC1 is unique in that it subdivides B-1a cells into PC1hi and PC1lo subpopulations with distinct functions, such as production of natural IgM and gut IgA, response to the pneumococcal antigen PPS-3, secretion of interleukin (IL)-10, and support for T helper 1 (TH1) cell differentiation. RNA sequencing (RNA-seq) of these subsets revealed differential expression of genes involved in cellular movement and immune cell trafficking. We will discuss these new insights underlying the heterogeneous nature of the B-1a cell repertoire.