Transcriptional profiling of antigen-dependent murine B cell differentiation and memory formation
Transcriptional profiling of antigen-dependent murine B cell differentiation and memory formation
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DOI：
10.4049/jimmunol.179.10.6808
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发表时间：
2007-11-15
影响因子：
4.4
通讯作者：
Weissman, Irving L.
中科院分区：
文献类型：
--
作者：
Bhattacharya, Deepta;Cheah, Ming T.;Weissman, Irving L.
体液免疫的特征在于产生分泌Ab的浆细胞和记忆B细胞，其在暴露于Ag时可以比它们的幼稚对应物更快速地产生特异性Ab。为了确定区分幼稚和记忆B细胞的内在差异，并确定允许生发中心B细胞分化为记忆B细胞的途径，我们比较了这三种细胞类型的高度纯化群体的转录谱沿着从用T依赖性Ag免疫的小鼠中分离的浆细胞。记忆B细胞的转录谱与幼稚B细胞的转录谱相似，但显示出几个重要的差异，包括活化诱导的脱氨酶和几个抗凋亡基因、趋化受体和共刺激分子的表达增加。逆转录病毒表达Klf2或Ski，这两种转录调节因子在记忆B细胞中相对于其生发中心前体特异性富集，在体外赋予Ag受体和CD 40接合的B细胞竞争优势。这些数据表明，由于记忆B细胞表达独特的转录程序，不道德回忆反应比初级反应更快，这使得它们既能保持高频率，又能检测并快速响应抗原再暴露。
Humoral immunity is characterized by the generation of Ab-secreting plasma cells and memory B cells that can more rapidly generate specific Abs upon Ag exposure than their naive counterparts. To determine the intrinsic differences that distinguish naive and memory B cells and to identify pathways that allow germinal center B cells to differentiate into memory B cells, we compared the transcriptional profiles of highly purified populations of these three cell types along with plasma cells isolated from mice immunized with a T-dependent Ag. The transcriptional profile of memory B cells is similar to that of naive B cells, yet displays several important differences, including increased expression of activation-induced deaminase and several antiapoptotic genes, chemotactic receptors, and costimulatory molecules. Retroviral expression of either Klf2 or Ski, two transcriptional regulators specifically enriched in memory B cells relative to their germinal center precursors, imparted a competitive advantage to Ag receptor and CD40-engaged B cells in vitro. These data suggest that Immoral recall responses are more rapid than primary responses due to the expression of a unique transcriptional program by memory B cells that allows them to both be maintained at high frequencies and to detect and rapidly respond to antigenic re-exposure.