Yang Zhiyong, Robinson Marcus J, Chen Xiangjun, Smith Geoffrey A, Taunton Jack, Liu Wanli, Allen Christopher D C
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, United States.
Elife. 2016 Dec 9;5:e21238. doi: 10.7554/eLife.21238.
IgE can trigger potent allergic responses, yet the mechanisms regulating IgE production are poorly understood. Here we reveal that IgE B cells are constrained by chronic activity of the IgE B cell receptor (BCR). In the absence of cognate antigen, the IgE BCR promoted terminal differentiation of B cells into plasma cells (PCs) under cell culture conditions mimicking T cell help. This antigen-independent PC differentiation involved multiple IgE domains and Syk, CD19, BLNK, Btk, and IRF4. Disruption of BCR signaling in mice led to consistently exaggerated IgE germinal center (GC) B cell but variably increased PC responses. We were unable to confirm reports that the IgE BCR directly promoted intrinsic apoptosis. Instead, IgE GC B cells exhibited poor antigen presentation and prolonged cell cycles, suggesting reduced competition for T cell help. We propose that chronic BCR activity and access to T cell help play critical roles in regulating IgE responses.
免疫球蛋白E（IgE）能够引发强烈的过敏反应，然而，调节IgE产生的机制却鲜为人知。在此，我们揭示IgE B细胞受到IgE B细胞受体（BCR）慢性活性的限制。在缺乏同源抗原的情况下，IgE BCR在模拟T细胞辅助的细胞培养条件下促进B细胞终末分化为浆细胞（PC）。这种不依赖抗原的PC分化涉及多个IgE结构域以及脾酪氨酸激酶（Syk）、CD19、B细胞连接蛋白（BLNK）、布鲁顿酪氨酸激酶（Btk）和干扰素调节因子4（IRF4）。小鼠体内BCR信号的破坏导致IgE生发中心（GC）B细胞持续过度增殖，但浆细胞反应却有不同程度的增加。我们无法证实IgE BCR直接促进内在凋亡的报道。相反，IgE GC B细胞表现出较差的抗原呈递能力和延长的细胞周期，这表明其对T细胞辅助的竞争减少。我们认为，BCR的慢性活性和获得T细胞辅助在调节IgE反应中起着关键作用。
