Memory B cell commitment, maintenance and terminal differentiation

记忆 B 细胞定型、维持和终末分化

基本信息

批准号：
16043261
负责人：
TAKEMORI Toshitada
金额：
$ 25.34万
依托单位：
RIKEN (2006)National Institute of Infectious Diseases (2004-2005)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

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

记忆 B 细胞获得了一些与 na・e B 细胞不同的内在特性，这表明记忆 B 细胞可能具有与其他阶段的 B 细胞在数量和/或质量上不同的独特基因表达。 B 细胞在抗原再暴露后的定型、存活和终末分化，我们鉴定了在抗原刺激下从初始 B 细胞向 GC B 细胞、记忆 B 细胞或浆细胞转变过程中发生的基因表达变化。在记忆 B 细胞中高度表达，包括E52和4010。E52被证明是运动神经元存活基因(SMN)1的人类同源物，该基因是脊髓性肌萎缩症(SMA)的致病基因。SMN在B细胞淋巴瘤细胞系中过度表达。细胞在促凋亡培养条件下的存活，提出了该基因可能负责记忆 B 细胞存活的想法，因此，我们通过生化分析确定了 SMN 在细胞存活中的作用并得出结论。 SMN 延长了细胞在氧化应激下的存活时间，并增强了线粒体呼吸链复合物 I 的活性。4010 基因编码一种采纳分子，其在脾 B 细胞中的过度表达导致抗 Igs 和抗-Ig 刺激后 IgG1 反应增强。体外 CD40 mAb 因此，4010 可能参与负责记忆 B 细胞终末分化或抗体分泌的信号级联。为了了解负责记忆 B 细胞定向的调控网络，我们利用 Affymetrix GeneChip 分析并表征了抗原刺激下从初始 B 细胞向 GC B 细胞、记忆 B 细胞或浆细胞转变过程中基因表达的变化。 Q-PCR 证实表明，记忆 B 细胞群表达了一组在该群体中选择性富集的转录物，其表达模式具有类似的时间依赖性变化。为了利用记忆 B 细胞谱系的此类遗传标记，我们分析了早期事件。抗原特异性B细胞反应并表明，至少在免疫后第 5 天至第 6 天，活化的 B 细胞会进展为记忆 B 细胞，并伴有类别转换重组和有效增殖。

项目成果

期刊论文数量（29）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A unique role of Ras in memoryB cell response.

Ras 在记忆 B 细胞反应中的独特作用。

DOI：
发表时间：
2005
期刊：
Immunity 23
影响因子：
0
作者：
Takahashi;Y;Inamine A;Hashimoto;S.-I;Yoshioka;E;Kojima;N;Abe;R;Takemroi T.
通讯作者：
Takemroi T.

An essentialrole for the RNA-pr b GANP for somatic hypermu tation of immunoglobulin gene in germinal center B cells.

RNA-pr b GANP 在生发中心 B 细胞免疫球蛋白基因体细胞超突变中发挥重要作用。

DOI：
发表时间：
2004
期刊：
Pric, Natl. Acad. Sci. USA 101
影响因子：
0
作者：
Kuwahara;K;Fujita;S;Takahashi;Y;Xing;Y;Nakagata;N;Takemori;T;Aizawa;S;Sakaguchi;N.
通讯作者：
N.

B7-H1-induced apoptosis as a mechanism of immune privilege of corneal allografts

DOI：
10.4049/jimmunol.177.9.5928
发表时间：
2006-11-01
期刊：
JOURNAL OF IMMUNOLOGY
影响因子：
4.4
作者：
Hori, Junko;Wang, Mingcong;Azuma, Miyuki
通讯作者：
Azuma, Miyuki

Interferon regulatory factor-4 negatively regulates the product of proinfalmmatory cytokines by macrophages in response to LPS.

干扰素调节因子 4 负向调节巨噬细胞响应 LPS 产生的促炎症细胞因子的产物。

DOI：
发表时间：
2005
期刊：
Proc. Natl. Acad. Sci. USA 102
影响因子：
0
作者：
Honnma;K;Udono;H;Ohkusu-Tsukada;K;Khono;T;Yamamoto;K;Ogawa;A;Takemori;T;Kumatori;A;Suzuki;S;Matsuyama;T;Yui;K.
通讯作者：
K.

Analysis of anti-SRAS corona virus response in mice inoculated with UV-irradiated virus.

接种紫外线照射病毒的小鼠的抗 SRAS 冠状病毒反应分析。