Increased expression of CD27 on activated human memory B cells correlates with their commitment to the plasma cell lineage
Increased expression of CD27 on activated human memory B cells correlates with their commitment to the plasma cell lineage
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DOI：
10.4049/jimmunol.174.7.4034
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发表时间：
2005-04-01
影响因子：
4.4
通讯作者：
Tangye, SG
中科院分区：
文献类型：
--
作者：
Avery, DT;Ellyard, JI;Tangye, SG
浆细胞（PC）或Ig分泌细胞（ISC）是负责产生保护性IG的终末分化的B细胞。ISC可以通过用T细胞衍生的刺激物CD 40 L、IL-2和IL-10培养人B细胞来体外产生。ISC传统上通过增加的CD 38（类似于原代人PC）表达和获得的分泌IG的能力来鉴定。通过跟踪活化B细胞的增殖历史，我们先前报道了记忆B细胞向CD 38（+）B细胞的分化是IL- 10依赖性的，并且随着细胞分裂频率增加。然而，<50%的CD 38（+）细胞分泌IG，并且存在CD 38（-）ISC群体。因此，体外产生的CD 38（+）细胞的PC表型与PC功能无关。为了解决这个问题，我们已经检查了激活的记忆B细胞的培养物，以准确地鉴定体外产生的ISC的表型。我们发现，记忆B细胞上的CD 27也以IL-10依赖性和分裂依赖性方式上调，并且ISC分离到活化的记忆B细胞的CD 27高亚群中，而与获得的CD 38表达无关。在这些培养物中产生的ISC表达水平升高的转录因子Blimp-1和X盒结合蛋白-1和Pax-5水平降低，并表现出向CXCL 12的选择性迁移，类似于原代PC。我们认为记忆B细胞向PC的分化涉及一个过渡阶段，其特征是具有获得性分泌高水平IG的能力的CD 27（高）CD 38（-）表型。
Plasma cells (PC) or Ig-secreting cells (ISC) are terminally differentiated B cells responsible for the production of protective Ig. ISC can be generated in vitro by culturing human B cells with the T cell-derived stimuli CD40L, IL-2, and IL-10. ISC have traditionally been identified by the increased expression of CD38, analogous to primary human PC, and the acquired ability to secrete Ig. By tracking the proliferation history of activated B cells, we previously reported that the differentiation of memory B cells into CD38(+) B cells is IL- 10 dependent, and increases in frequency with cell division. However, < 50 % of CD38(+) cells secreted Ig, and there was a population of CD38(-) ISC. Thus, the PC phenotype of CD38(+) cells generated in vitro did not correlate with PC function. To address this, we have examined cultures of activated memory B cells to accurately identify the phenotype of ISC generated in vitro. We found that CD27 is also up-regulated on memory B cells in an IL-10-dependent and division-dependent manner, and that ISC segregated into the CD27 high subset of activated memory B cells irrespective of the acquired expression of CD38. The ISC generated in these cultures expressed elevated levels of the transcription factors Blimp-1 and X box-binding protein-1 and reduced levels of Pax-5, and exhibited selective migration toward CXCL12, similar to primary PC. We propose that the differentiation of memory B cells into PC involves a transitional stage characterized by a CD27(high)CD38(-) phenotype with the acquired ability to secrete high levels of Ig.