一个标志性的人类自身抗体的致病进化中的淋巴瘤驱动突变
Mandeep Singh1, Katherine J L Jackson1, Jing J Wang2
1The Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
Cell
|February 16, 2020
概括
产生类风湿因子自身抗体的流B细胞与淋巴细胞恶性瘤有共同的机制. 这些细胞累积突变,导致血管炎的致病性自身抗体,并揭示了淋巴发育的癌前阶段.
科学领域:
- 免疫学
- 癌症学
- 遗传学
背景情况:
- 病原性自身抗体是自身免疫性疾病的标志,但它们的细胞起源和逃避免疫检查点仍然不清楚.
- 混合型冷球蛋白性血管炎与致病性类风湿因子自身抗体有关,但潜在的细胞机制尚未完全理解.
研究的目的:
- 研究致病性自身抗体产生与淋巴细胞恶性瘤之间的共享机制.
- 了解生产自身抗体的B细胞如何逃避免疫检查点.
主要方法:
- 单细胞多组分析,包括DNA和RNA测序.
- 血清抗体测序和抗体合成
- 对B细胞克隆树和体质突变的分析.
主要成果:
- 罕见的循环B淋巴细胞产生病原性自身抗体,形成具有累积突变的克隆树.
- 这些B细胞在控制增殖和V(D) J突变的基因中存在淋巴瘤驱动突变 (例如,CARD11,TNFAIP3,CCND3).
- 抗体V(D) J突变通过在较低的温度下诱导自身抗体的聚合来驱动病原性.
结论:
- 在自身抗体产生和淋巴细胞恶性瘤之间存在一种共同的机制,涉及克隆扩张和体质突变.
- 这项研究确定了人类淋巴发育的前新生阶段.
- 自体抗体的体质突变导致它们的聚合,并导致疾病的发病.
更多相关视频
相关概念视频
Antigens Involved in Adaptive Immunity
1.2K
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and...
Complete Antigens
Complete antigens possess both immunogenicity and...
1.2K
B Cell Activation and Differentiation
15.7K
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...
15.7K
Diversity of Antigen Receptors
1.3K
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...
1.3K
Cancers Originate from Somatic Mutations in a Single Cell
14.4K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
14.4K
The Intrinsic Apoptotic Pathway
8.1K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.1K
Mismatch Repair
6.2K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
6.2K


