激活诱导的cytidine脱氨酶会在混合体中激活体质突变
Alberto Martin1, Philip D Bardwell, Caroline J Woo
1Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue Chanin 403, Bronx, New York 10461, USA.
Nature
|February 2, 2002
概括
身体突变 (SHM) 产生高亲和力的抗体. 这项研究表明,激活诱导的cytidine脱胺酶 (AID) 可以在B细胞中诱导SHM,即使没有中枢细胞特异性因素.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 身体突变 (SHM) 对于通过V区域基因多样化产生高亲和度抗体至关重要.
- SHM发生在B细胞分化的中枢细胞阶段,涉及点突变.
- 激活诱导的cytidine去氨酶 (AID) 对SHM至关重要,但其确切的作用尚不清楚.
研究的目的:
- 调查AID在体质突变中的作用.
- 为了确定单独的AID表达是否可以在B细胞中诱导SHM.
- 为了确定AID介导的SHM所需的潜在的辅助因子.
主要方法:
- 利用了拉莫斯细胞 (类似于细胞中心细胞) 和杂交瘤细胞 (后来的分化阶段).
- 评估了在拉莫斯细胞中对SHM的AID要求.
- 在混合瘤细胞中表达了AID,以观察SHM诱导.
- 分析了AID诱导的SHM中的突变模式.
主要成果:
- AID被证实是Ramos细胞中SHM所必需的.
- 仅AID的表达就足以在混合瘤细胞中诱导SHM.
- 杂交瘤中的突变主要是在RGYW或WRCY动机内的G*C基对中,这表明了AID的直接作用.
- 在杂交瘤中激活了SHM,这表明AID可能不需要中枢细胞特异性辅因子.
结论:
- 艾滋病是体质突变的主要驱动因素.
- 艾滋病可以诱导SHM独立于其他心脏细胞特异性因素.
- 这些发现表明,AID可能单独或与无处不在的表达因子一起起作用,以调解SHM.
相关概念视频
01:30Spontaneous and Induced Mutations
2.9K
Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).
2.9K
01:31Hybridoma Technology
18.5K
Hybridoma technology is used for the large-scale production of monoclonal antibodies. Monoclonal antibodies bind to only a single antigenic determinant or epitope. Such antibodies are used in research, diagnostics, and disease therapy. The hybridoma technology established in 1975 by Georges Köhler and Cesar Milstein was awarded the Nobel Prize in Medicine in 1984 for revolutionizing research and therapy.
Hybridoma Selection
Commonly used fusion techniques — electroporation,...
Hybridoma Selection
Commonly used fusion techniques — electroporation,...
18.5K
01:24B Cell Activation and Differentiation
18.3K
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...
18.3K
02:08Gene Conversion
10.9K
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
10.9K
01:24Methods of Nuclear Reprogramming
2.3K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
2.3K