Molecular mechanism for memory B cell dynamics and survival

记忆 B 细胞动力学和存活的分子机制

• 批准号: 15390164
• 负责人: TAKEMORI Toshitada
• 金额: $ 9.6万
• 依托单位: NATIONAL INSTITUTE OF INFECTIOUS DISEASES
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390164/
• 关键词: memory B cells; Germinal center; somatic mutations; survival; apoptosis; Ras; affinity selection; スフィンゴシン-1-リン酸; 細胞死抵抗性; inportinβ3; PRMT6; SMN exon7; 変異マウス; 胚中心B細胞; 長期生存抗体産生細胞; アポトーシス

Chemotactic chemokines play important role in the selective recruitment of B cells to different histological tissues, establishing B cell homeostasis and immune response. Here we report that CC chemokine receptor D6 and CCR1 is differentially expressed on MZ and memory B cells in the spleen and B1 cells in the peritoneal cavity. In agreement with previous observations, D6 on B cell subsets physically interact with its ligands, internalize, and target them intracellular degradation, whereasa it did not cause activation of MZ B cells and B1 cells, such as proliferation, terminal differentiation. The results suggest that the genuine function of D6 on B cell subsets is to eliminate CC chemokines from microenvironment surrounding MZ B cell and B1 cells. In addition, during the course of search for memory B cells' specific genes, we have identified the gene 3940 who express at high levels in memory cells and marginal zone B cells. Over expression of 3940 in B cell lymphoma cell lines resulted in the prolongation of cell survival under the pro-apoptoic conditions, suggesting that 3940 may play some role in survival of memory B cells.

趋化性趋化因子在B细胞向不同组织的选择性募集、建立B细胞稳态和免疫应答中起重要作用。在这里，我们报告CC趋化因子受体D6和CCR 1的差异表达MZ和记忆B细胞在脾脏和B1细胞在腹腔。与以前的观察结果一致，B细胞亚群上的D6与其配体发生物理相互作用，内化并靶向其细胞内降解，但它不引起MZ B细胞和B1细胞的活化，如增殖、终末分化。结果提示，D6对B细胞亚群的真正作用是清除MZ B细胞和B1细胞周围微环境中的CC趋化因子。另外，在寻找记忆B细胞特异性基因的过程中，我们已经鉴定了在记忆细胞和边缘区B细胞中高水平表达的基因3940。在B细胞淋巴瘤细胞系中过表达3940导致在促凋亡条件下细胞存活的延长，表明3940可能在记忆B细胞的存活中起一定作用。

项目成果

Studies on the generation and maintenance of mucosal Cytotoxic T Lymphocytes against human immunodeficiency virus type-1 Gag in mice.

小鼠体内针对人类免疫缺陷病毒 1 型 Gag 的粘膜细胞毒性 T 淋巴细胞的产生和维持的研究。

• 发表时间: 2003
• 期刊: Aids Res. Hum. Retro. 19
• 作者: Yoshizawa;I.;et al.
• 通讯作者: et al.

A unique role of Ras in memoryB cell response.

Ras 在记忆 B 细胞反应中的独特作用。

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

An essential role for the RNA-pr b GANP for somatic hypermutation of immunoglobulin gene in genninal center B cells.

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

• 发表时间: 2004
• 期刊: Proc. NatI. Acad. Sci. USA 101
• 作者: Kuwahara;K. et al.
• 通讯作者: K. et al.

Immunological detection of severe acute respiratory syndrome coronavirus by monoclonal antibodies.

单克隆抗体对严重急性呼吸综合征冠状病毒的免疫学检测。

• 发表时间: 2005
• 期刊: Japanese Journal of Infectious Diseases 58
• 作者: Ohnishi;K.;Sakaguchi;M.;Kaji;T.;Akagawa;K.;Taniyama;T.;Kasai;M.;Tsunetsugu-Yokota;Y.;Oshima;M.;Yamamoto;K.;Takasuka;N.;Hashimoto;S.;Ato;M.;Fujii;H.;Takahashi;Y.;Morikawa;S.;Ishii;K.;Sata;T.;Takagi;H.;Itamura;S.;Odagir
• 通讯作者: Odagir

Two waves of memory B-cell generation in the primary immune response

• DOI: 10.1093/intimm/dxh241
• 发表时间: 2005-05-01
• 期刊: INTERNATIONAL IMMUNOLOGY
• 影响因子: 4.4
• 作者: Inamine, A;Takahashi, Y;Abe, R
• 通讯作者: Abe, R