生发中心
生物
亲和力成熟
免疫原
体细胞
免疫系统
细胞生物学
抗体
体细胞突变
B细胞
受体
突变
克隆选择
免疫学
分子生物学
遗传学
单克隆抗体
基因
作者
Thomas Hägglöf,Melissa Cipolla,Maximilian Loewe,Spencer Chen,Luka Mesin,Harald Hartweger,Mohamed ElTanbouly,Alice Cho,Anna Gazumyan,Víctor Ramos,Leonidas Stamatatos,Thiago Y. Oliveira,Michel C. Nussenzweig,Charlotte Viant
出处
期刊:Cell
[Elsevier]
日期:2023-01-01
卷期号:186 (1): 147-161.e15
被引量:26
标识
DOI:10.1016/j.cell.2022.11.032
摘要
Antibody responses are characterized by increasing affinity and diversity over time. Affinity maturation occurs in germinal centers by a mechanism that involves repeated cycles of somatic mutation and selection. How antibody responses diversify while also undergoing affinity maturation is not as well understood. Here, we examined germinal center (GC) dynamics by tracking B cell entry, division, somatic mutation, and specificity. Our experiments show that naive B cells continuously enter GCs where they compete for T cell help and undergo clonal expansion. Consistent with late entry, invaders carry fewer mutations but can contribute up to 30% or more of the cells in late-stage germinal centers. Notably, cells entering the germinal center at later stages of the reaction diversify the immune response by expressing receptors that show low affinity to the immunogen. Paradoxically, the affinity threshold for late GC entry is lowered in the presence of high-affinity antibodies.
科研通智能强力驱动
Strongly Powered by AbleSci AI