通过MIZ1-TMBIM4调节BCR介导的Ca2+调动,可以保护IgG1+GCB细胞阳性选择
Lingling Zhang1, Amparo Toboso-Navasa1, Arief Gunawan1
1Immunity and Cancer, Francis Crick Institute, London, UK.
Science immunology
|April 5, 2024
概括
与IgM+B细胞不同的是,MIZ1对于IgG1+B细胞在生殖中心的生存至关重要. 这种转录因子调节信号传递,以防止抗体成熟期间的细胞死亡.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 生殖中心 (GCs) 对抗体亲和力成熟和同型从IgM切换到IgG至关重要.
- 在GC中控制异型特异性选择的机制仍然不完全理解.
- 了解GCB细胞选择是改善幽默免疫和疫苗反应的关键.
研究的目的:
- 调查异型特异性阳性选择在生殖中心B细胞的转录调节.
- 确定在亲和力成熟过程中对IgG1+B细胞生存至关重要的转录因子.
- 阐明基因细胞中IgG1+B细胞选择的分子机制.
主要方法:
- 在小鼠模型中使用CRISPR-Cas9选.
- 条件小鼠遗传学研究基因功能 in vivo.
- 对B细胞受体 (BCR) 信号和 (Ca2+) 调动的分析.
- 在GC B细胞中评估线粒体功能和亡.
主要成果:
- MIZ1被确定为IgG1+GC B细胞存活所需的关键转录因子.
- IgM+ GC B 细胞表现出独立于 MIZ1 介导的生存信号.
- MIZ1诱导TMBIM4,它调节IP3R介导的Ca2+流向BCR信号的下游.
- MIZ1-TMBIM4通路保护IgG1+ GC B细胞免受过度的Ca2+积累和线粒体功能障碍引起的死亡.
结论:
- 一个新的MIZ1-TMBIM4轴决定了在GC选择期间IgG1+B细胞的存活率.
- 这种机制突出显示了GC阳性选择中的异型特异性依赖性.
- 这些发现揭示了调节幽默免疫和B细胞命运的新途径.
相关概念视频
01:24B Cell Activation and Differentiation
1.7K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
1.7K
01:15Receptor Downregulation in MVBs
2.1K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.1K
01:16Calmodulin-dependent Signaling
5.1K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.1K
01:22T Cell Activation and Clonal Selection
721
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
721
01:28Diversity of Antigen Receptors
582
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
582
01:31Immunoglobulin-like Cell Adhesion Molecules
3.3K
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
3.3K