Lee Jisoo, Kuchen Stefan, Fischer Randy, Chang Sooghee, Lipsky Peter E
Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
J Immunol. 2009 Apr 1;182(7):4116-26. doi: 10.4049/jimmunol.0803391.
We have identified a distinct pre-naive B cell population circulating in human peripheral blood that exhibits an intermediate phenotype between transitional and naive B cells. Like human transitional B cells, these cells express CD5 but have intermediate densities of CD38, CD10, CD9, and the ABCB1 transporter compared with transitional and naive B cells. These pre-naive B cells account for a majority of circulating human CD5(+) B cells. Importantly, CD5(+) pre-naive B cells could be induced to differentiate into cells with a naive phenotype in vitro. CD5(+) pre-naive B cells show only partial responses to BCR stimulation and CD40 ligation and undergo more spontaneous apoptosis and cell death than do naive B cells, whereas BAFF/BLyS (B cell-activating factor belonging to the TNF family) did not enhance their survival compared with naive B cells. In contrast, CD5(+) pre-naive B cells carry out certain functions comparable to naive B cells, including the capacity to differentiate into plasma cells and the ability to function as APCs. Notably, an increased proportion of CD5(+) pre-naive B cells were found in peripheral blood of patients with systemic lupus erythematosus. These results have identified a unique intermediate in human naive B cell development within the peripheral blood and derangements of its homeostasis in patients with systemic lupus erythematosus.
我们已鉴定出一种在人外周血中循环的独特的前幼稚B细胞群体，其表现出介于过渡性B细胞和幼稚B细胞之间的中间表型。与人类过渡性B细胞一样，这些细胞表达CD5，但与过渡性B细胞和幼稚B细胞相比，其CD38、CD10、CD9和ABCB1转运蛋白的密度处于中间水平。这些前幼稚B细胞占循环中的人类CD5(+) B细胞的大多数。重要的是，CD5(+)前幼稚B细胞在体外可被诱导分化为具有幼稚表型的细胞。CD5(+)前幼稚B细胞对BCR刺激和CD40连接仅表现出部分反应，并且比幼稚B细胞经历更多的自发凋亡和细胞死亡，而与幼稚B细胞相比，BAFF/BLyS（肿瘤坏死因子家族的B细胞激活因子）并未提高其存活率。相比之下，CD5(+)前幼稚B细胞执行某些与幼稚B细胞相当的功能，包括分化为浆细胞的能力和作为抗原呈递细胞发挥作用的能力。值得注意的是，在系统性红斑狼疮患者的外周血中发现CD5(+)前幼稚B细胞的比例增加。这些结果已确定了外周血中人类幼稚B细胞发育过程中的一种独特中间体，以及系统性红斑狼疮患者体内其稳态的紊乱。
