澳大利亚墨尔本大学Philip D. Hodgkin和Miles B. Horton共同合作近期取得重要工作进展。他们通过谱系追踪显示B细胞抗体类型转换是随机的、细胞自主的和可调节的。相关研究成果2022年9月14日在线出版于《免疫学》杂志上。

通过在分化的B细胞克隆中追踪单个细胞的谱系，研究人员确定了离散命运控制机制的遗传性，从而为B细胞命运调控的一般数学模型提供信息。起始细胞高度影响克隆浆细胞的命运，而类转换重组（CSR）在克隆中是多种多样的。反过来，这些CSR模式是由激活诱导的胞苷脱氨酶（AID）和IgH种系转录（GLT）独立的全有或全无的表达引起的，后者在每次细胞分裂后随机重新表达。以这些分子转换规则为前提的随机模型准确地预测了体外不同条件下和体内免疫反应期间的抗体转换结果。因此，功能多样的抗体类型的产生遵循自主细胞编程的规则，可以通过调整和建模以合理控制抗体类别获得潜在的治疗效益。

据介绍，为了优化对病原体的免疫力，B淋巴细胞产生具有功能多样化抗体同型的浆细胞。

附：英文原文

Title: Lineage tracing reveals B cell antibody class switching is stochastic, cell-autonomous, and tuneable

Author: Miles B. Horton, HoChan Cheon, Ken R. Duffy, Daniel Brown, Shalin H. Naik, Carolina Alvarado, Joanna R. Groom, Susanne Heinzel, Philip D. Hodgkin

Issue&Volume: 2022-09-14

Abstract: To optimize immunity to pathogens, B lymphocytes generate plasma cells with functionallydiverse antibody isotypes. By lineage tracing single cells within differentiatingB cell clones, we identified the heritability of discrete fate controlling mechanismsto inform a general mathematical model of B cell fate regulation. Founder cells highlyinfluenced clonal plasma-cell fate, whereas class switch recombination (CSR) was variegatedwithin clones. In turn, these CSR patterns resulted from independent all-or-none expressionof both activation-induced cytidine deaminase (AID) and IgH germline transcription (GLT), with the latter being randomly re-expressed after eachcell division. A stochastic model premised on these molecular transition rules accuratelypredicted antibody switching outcomes under varied conditions in vitro and during an immune response in vivo. Thus, the generation of functionally diverse antibody types follows rules of autonomouscellular programming that can be adapted and modeled for the rational control of antibodyclasses for potential therapeutic benefit.

DOI: 10.1016/j.immuni.2022.08.004

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00397-1