美国弗朗西斯·克里克研究所Pavel Tolar团队近日取得一项新成果。经过不懈努力，他们发现IgE⁺ B细胞中缓释钙信号限制了浆细胞的分化和存活。2021年12月7日，国际学术期刊《免疫学》发表了这一成果。

为了更好地了解IgE^-BCR介导的IgE反应调控，研究人员进行了全基因组CRISPR筛选，可以比较IgE⁺和IgG1⁺ B细胞对增殖、存活和分化为长寿浆细胞(PC)的需求。IgE⁺ PC表现出对PI3K-mTOR通路的依赖性，这会增加转录因子IRF4的蛋白质含量。相比之下，钙-钙调神经磷酸酶-NFAT通路组分的缺失促进了IgE⁺ PC的分化。带有B细胞特异性钙调神经磷酸酶B1缺失的小鼠具有IgE⁺ PC增加的表型。

从机制上讲，IgE^-BCR下游IgE⁺ PC 中细胞内钙离子的持续升高促进了BCL2L11依赖性细胞凋亡。因此，IgE^-BCR下游的长时钙信号控制着IgE反应的自限性，并且可能与过敏性疾病中产生的IgE细胞积累有关。

据了解，与其他抗体同型相比，B细胞可瞬时转化为产生IgE的细胞，而不会产生PC或记忆B细胞。

附：英文原文

Title: Chronic calcium signaling in IgE+ B cells limits plasma cell differentiation and survival

Author: Rebecca Newman, Pavel Tolar

Issue&Volume: 2021-12-07

Abstract: In contrast to other antibody isotypes, B cells switched to IgE respond transiently and do not give rise to long-lived plasma cells (PCs) or memory B cells. To better understand IgE-BCR-mediated control of IgE responses, we developed whole-genome CRISPR screening that enabled comparison of IgE+ and IgG1+ B cell requirements for proliferation, survival, and differentiation into PCs. IgE+ PCs exhibited dependency on the PI3K-mTOR axis that increased protein amounts of the transcription factor IRF4. In contrast, loss of components of the calcium-calcineurin-NFAT pathway promoted IgE+ PC differentiation. Mice bearing a B cell-specific deletion of calcineurin B1 exhibited increased production of IgE+ PCs. Mechanistically, sustained elevation of intracellular calcium in IgE+ PCs downstream of the IgE-BCR promoted BCL2L11-dependent apoptosis. Thus, chronic calcium signaling downstream of the IgE-BCR controls the self-limiting character of IgE responses and may be relevant to the accumulation of IgE-producing cells in allergic disease.

DOI: 10.1016/j.immuni.2021.11.006

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00497-0