由TIM-1和TIGIT的表达定义的人类调节性记忆B细胞在多发性硬化症中是功能失调的
Johnna F Varghese1,2, Belinda J Kaskow1,2, Felipe von Glehn1,2
1Harvard Medical School, Boston, MA, United States.
Frontiers in immunology
|May 15, 2024
概括
表达TIM-1和TIGIT的调节性B细胞 (Bregs) 对于免疫抑制至关重要. 在多发性硬化症 (MS) 中,这些细胞功能受损,影响疾病调节和治疗反应.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 神经免疫学 神经免疫学
背景情况:
- 调控性B细胞 (Bregs) 对于免疫抑制至关重要,但缺乏确定的标记物.
- 在B细胞上的TIM-1和TIGIT表达与多发性硬化症 (MS) 鼠标模型中的自我耐受性和中枢神经系统自身免疫性有关.
研究的目的:
- 研究表达TIM-1和TIGIT的人类记忆B细胞的调节功能.
- 为了比较这些B细胞子集在健康捐赠者 (HC) 和复发性复发性 (RR) MS患者中的活动.
主要方法:
- 用FACS排序的B (memB) 记忆细胞子集 (TIM-1+/-TIGIT+/-) 与全基CD4+ T细胞共同培养.
- 分析了T细胞的增殖,炎症标志物诱导和细胞因子的产生.
- 使用SMARTSeq2RNA测序评估了转录差异.
主要成果:
- TIM-1+TIGIT+双阳性 (DP) memB细胞表现出调控活性,将其确定为Breg群体.
- 与健康对照组相比,MS患者的DP Bregs的抑制作用较小.
- 转录组分析揭示了MS衍生的DP Bregs中明显的基因表达,T细胞激活和生存基因表达增加.
- 治疗后的DP memB细胞频率与抗CD20治疗反应相关.
结论:
- TIM-1/TIGIT表达式定义了具有独特功能的独特内存B细胞子集.
- 同时表达TIM-1和TIGIT识别了一种调节性B细胞子集,该子集在MS中功能受损.
相关概念视频
T Cell Types and Functions
1.0K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.0K
B 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
T Cell Activation and Clonal Selection
709
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...
709


