Heme regulates B-cell differentiation, antibody class switch, and heme oxygenase-1 expression in B cells as a ligand of Bach2
Heme regulates B-cell differentiation, antibody class switch, and heme oxygenase-1 expression in B cells as a ligand of Bach2
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DOI：
10.1182/blood-2010-07-296483
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发表时间：
2011-05-19
期刊：
影响因子：
20.3
通讯作者：
Igarashi, Kazuhiko
中科院分区：
文献类型：
--
作者：
Watanabe-Matsui, Miki;Muto, Akihiko;Igarashi, Kazuhiko
血红素与蛋白质结合以调节其功能，从而在各种生物事件中充当信号分子。我们发现，血红素结合Bach 2，一个转录因子的体液免疫，包括抗体类转换必不可少的。血红素在体外抑制Bach 2的DNA结合活性，并缩短其在B细胞中的半衰期。当添加到B细胞原代培养物中时，血红素增强了Blimp-1（浆细胞的主要调节因子）的转录，并使浆细胞分化向IgM同种型倾斜，降低了体外IgG水平。小鼠腹腔注射血红素时，血红素与抗原同时给药，但不与抗原暴露后给药，抑制抗原特异性IgM的产生，这表明血红素也调节B细胞对抗原的早期反应。在B细胞中，血红素加氧酶-1受血红素调节，同时受Bach 2和Bach 1的抑制。此外，血红素摄取基因的表达改变响应B细胞活化和血红素管理。我们的研究结果揭示了血红素作为Bach 2的配体和作为参与浆细胞分化的调节信号的新功能。（血。2011;117（20）：5438-5448）
Heme binds to proteins to modulate their function, thereby functioning as a signaling molecule in a variety of biologic events. We found that heme bound to Bach2, a transcription factor essential for humoral immunity, including antibody class switch. Heme inhibited the DNA binding activity of Bach2 in vitro and reduced its half-life in B cells. When added to B-cell primary cultures, heme enhanced the transcription of Blimp-1, the master regulator of plasma cells, and skewed plasma cell differentiation toward the IgM isotype, decreasing the IgG levels in vitro. Intraperitoneal injection of heme in mice inhibited the production of antigen-specific IgM when heme was administered simultaneously with the antigen but not when it was administered after antigen exposure, suggesting that heme also modulates the early phase of B-cell responses to antigen. Heme oxy-genase-1, which is known to be regulated by heme, was repressed by both Bach2 and Bach1 in B cells. Furthermore, the expression of genes for heme uptake changed in response to B-cell activation and heme administration. Our results reveal a new function for heme as a ligand of Bach2 and as a modulatory signal involved in plasma cell differentiation. (Blood. 2011;117(20):5438-5448)