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首页> 外文期刊>Nature immunology >Plasma cells require autophagy for sustainable immunoglobulin production
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Plasma cells require autophagy for sustainable immunoglobulin production

机译：浆细胞需要自噬才能持续产生免疫球蛋白

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摘要

The role of autophagy in plasma cells is unknown. Here we found notable autophagic activity in both differentiating and long-lived plasma cells and investigated its function through the use of mice with conditional deficiency in the essential autophagic molecule Atg5 in B cells. Atg5 -/- differentiating plasma cells had a larger endoplasmic reticulum (ER) and more ER stress signaling than did their wild-type counterparts, which led to higher expression of the transcriptional repressor Blimp-1 and immunoglobulins and more antibody secretion. The enhanced immunoglobulin synthesis was associated with less intracellular ATP and more death of mutant plasma cells, which identified an unsuspected autophagy-dependent cytoprotective trade-off between immunoglobulin synthesis and viability. In vivo, mice with conditional deficiency in Atg5 in B cells had defective antibody responses, complete selection in the bone marrow for plasma cells that escaped Atg5 deletion and fewer antigen-specific long-lived bone marrow plasma cells than did wild-type mice, despite having normal germinal center responses. Thus, autophagy is specifically required for plasma cell homeostasis and long-lived humoral immunity.
机译：自噬在浆细胞中的作用尚不清楚。在这里，我们在分化的和长寿的浆细胞中均发现了显着的自噬活性，并通过使用B细胞中必需的自噬分子Atg5有条件缺陷的小鼠来研究其功能。 Atg5-/-分化浆细胞比野生型对应细胞具有更大的内质网（ER）和更多的ER应激信号传导，从而导致转录阻遏物Blimp-1和免疫球蛋白的表达更高，抗体分泌更多。增强的免疫球蛋白合成与较少的细胞内ATP和更多的突变浆细胞死亡有关，这确定了免疫球蛋白合成与活力之间不可怀疑的自噬依赖性细胞保护权衡。在体内，与野生型小鼠相比，B细胞中Atg5有条件缺陷的小鼠具有缺陷的抗体反应，在骨髓中完全选择了逃避Atg5缺失的浆细胞，并且抗原特异性的长寿命骨髓浆细胞比野生型小鼠少生发中心反应正常。因此，自噬是浆细胞稳态和长寿命体液免疫所特有的。

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