Memory B cell commitment, maintenance and terminal differentiation

Memory B cells获取来自na·e B cells的不同的几个内在属性，建议Memory B cells可能有一个独特的基因表达，其中differers quantitatively and/or qualitatively from other stages of B cells。因此，要澄清对抗原释放上存储器B细胞提交、生存和终端差异的机制，我们可以在基因表达中识别出的变化，即从一个简单的B细胞到任何GC B细胞、存储器B细胞或等离子体细胞对抗原刺激的转变。我们已经克隆了几种基因，其中一些基因在存储器B细胞中被高度表达，包括E52和4010。E52被转化为发动机神经元基因生存的人类同源性（SMN）1，它是脊柱肌肉炎症的因果基因（SMA）。过度表达的SMN在B细胞淋巴瘤细胞线促进细胞存活在proapoptotic culture conditions中，提高基因可能对存储器B细胞存活负责的想法。因此，我们有责任。 ... More 通过生物化学分析和整合了SMN在细胞存活中的作用，使SMN延长的细胞存活在氧化应激和增强的反应链复合体中的活性I. 4010基因编码一个接受者分子及其过度表达在splenic B细胞中的结果在增强的IgG 1响应上对抗Igs和抗CD 40 mAb在体外刺激的增强。因此， 4010可以在信号级联中对每个存储器B细胞终端差异或抗体保密的响应。为了测试这一可能性，我们现在正在建立一个有条件的knock out mice.为了了解管理网络对内存B细胞提交的响应，我们使用Affymetrix基因芯片分析和表征基因表达中的改变，从简单的B细胞到GC B细胞，存储器B细胞或等离子体细胞对抗原刺激。Q-PCR确认表明，存储器B细胞的人口表达了一组转录被选择性地富集在这个人口中，并具有类似的时间依赖性变化在他们的表达模式中。为了有效地利用内存B细胞系列的遗传标记器，我们分析了抗原特异性B细胞响应的早期事件，并建议激活的B细胞进展到内存B细胞，至少在第5天至第6天免疫后，通过类交换机重组和有效生成来结合。Less（低）

Memory B cells acquire several intrinsic properties that differ from na・e B cells, suggesting that memory B cells may have a unique gene expression that differs quantitatively and/or qualitatively from other stages of B cells. Therefore, to clarify the mechanism responsible for memory B cell commitment, survival and terminal differentiation upon antigen reexposure, we identified changes in gene expression that occur in the transition from a naive B cell to either GC B cells, memory B cells or plasma cells upon antigen stimulation. We have cloned several genes which are highly expressed in memory B cells, including E52 and 4010. E52 was turned out to be a human homologue of the survival of motor neuron gene (SMN)1, which is a causative gene for spinal muscular atrophy (SMA). Over expression of SMN in B cell lymphoma cell lines prolonged cell survival in proapoptotic culture conditions, raising the idea that the gene could be responsible for memory B cell survival. Therefore, we characte … More rized the role of SMN in cell survival by biochemical analysis and concluded that SMN prolonged cell survival upon oxidant stress and enhanced the activity of the mitochondrial respiratory chain complex I.The 4010 gene encodes an adopter molecule and its overexpression in splenic B cells results in an augmentation of IgG1 response upon stimulation with anti-Igs and anti-CD40 mAbs in vitro. Thus, 4010 could be involved in the signaling cascade responsible for either memory B cell terminal differentiation or antibody secretion. To examine this possibility we are now establishing conditional knock out mice.To know the regulatory network responsible for memory B cell commitment, we utilized Affymetrix GeneChip analysis and characterize the changes in gene expression in the transition from naive B cells to GC B cells, memory B cells or plasma cells upon antigen stimulation. Q-PCR confirmation revealed that memory B cell population expressed a group of transcripts selectively enriched in this population, with similar time-dependent changes in their expression patterns. To utilize such genetic markers for the memory B cell lineage, we analyzed the early events in antigen-specific B cell response and suggested that activated B cells progress to memory B cells, at least, from day 5 to day 6 after immunization, accompanied by class-switch recombination and efficient proliferation. Less