He Jin-Shu, Subramaniam Sharrada, Narang Vipin, Srinivasan Kandhadayar, Saunders Sean P, Carbajo Daniel, Wen-Shan Tsao, Hidayah Hamadee Nur, Lum Josephine, Lee Andrea, Chen Jinmiao, Poidinger Michael, Zolezzi Francesca, Lafaille Juan J, Curotto de Lafaille Maria A
Singapore Immunology Network (SIgN), 8A Biomedical Grove, Singapore, 138648, Singapore.
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
Nat Commun. 2017 Sep 21;8(1):641. doi: 10.1038/s41467-017-00723-0.
The unique differentiation of IgE cells suggests unconventional mechanisms of IgE memory. IgE germinal centre cells are transient, most IgE cells are plasma cells, and high affinity IgE is produced by the switching of IgG1 cells to IgE. Here we investigate the function of subsets of IgG1 memory B cells in IgE production and find that two subsets of IgG1 memory B cells, CD80CD73 and CD80CD73, contribute distinctively to the repertoires of high affinity pathogenic IgE and low affinity non-pathogenic IgE. Furthermore, repertoire analysis indicates that high affinity IgE and IgG1 plasma cells differentiate from rare CD80CD73 high affinity memory clones without undergoing further mutagenesis. By identifying the cellular origin of high affinity IgE and the clonal selection of high affinity memory B cells into the plasma cell fate, our findings provide fundamental insights into the pathogenesis of allergies, and on the mechanisms of antibody production in memory B cell responses.IgE is an important mediator of protective immunity as well as allergic reaction, but how high affinity IgE antibodies are produced in memory responses is not clear. Here the authors show that IgE can be generated via class-switch recombination in IgG1 memory B cells without additional somatic hypermutation.
IgE细胞的独特分化提示了IgE记忆的非常规机制。IgE生发中心细胞是短暂的，大多数IgE细胞是浆细胞，高亲和力IgE是由IgG1细胞转换为IgE产生的。在这里，我们研究了IgG1记忆B细胞亚群在IgE产生中的功能，发现IgG1记忆B细胞的两个亚群，CD80CD73和CD80CD73，对高亲和力致病性IgE和低亲和力非致病性IgE的库有不同的贡献。此外，库分析表明，高亲和力IgE和IgG1浆细胞从罕见的CD80CD73高亲和力记忆克隆分化而来，而不经历进一步的诱变。通过确定高亲和力IgE的细胞起源以及高亲和力记忆B细胞向浆细胞命运的克隆选择，我们的发现为过敏症的发病机制以及记忆B细胞反应中抗体产生的机制提供了基本见解。IgE是保护性免疫以及过敏反应的重要介质，但记忆反应中高亲和力IgE抗体是如何产生的尚不清楚。在这里，作者表明IgE可以通过IgG1记忆B细胞中的类别转换重排产生，而无需额外的体细胞超突变。
