IgM antibodies to apoptosis-associated determinants recruit C1q and enhance dendritic cell phagocytosis of apoptotic cells.
IgM antibodies to apoptosis-associated determinants recruit C1q and enhance dendritic cell phagocytosis of apoptotic cells.
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与凋亡相关决定因素的IgM抗体募集C1Q并增强凋亡细胞的树突状细胞吞噬作用。
DOI：
10.4049/jimmunol.0804191
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发表时间：
2009-05-15
期刊：
影响因子：
--
通讯作者：
Silverman GJ
中科院分区：
文献类型：
--
作者：
Chen Y;Park YB;Patel E;Silverman GJ
天然抗体（Natural Abs）在无已知免疫暴露的情况下产生，已被描述能特异性识别凋亡细胞，但它们在天然免疫中的作用仍知之甚少。在此，我们表明对凋亡胸腺细胞上新抗原决定簇的免疫反应主要由针对氧化相关抗原的抗体所主导，这些抗原包括磷酸胆碱（PC）——一种在程序性细胞死亡过程中暴露的头部基团，以及丙二醛（MDA）——一种多不饱和脂质在暴露于活性氧化物质后产生的活性醛降解产物。虽然在未免疫的成年小鼠中针对凋亡细胞的天然抗体主要具有PC和MDA特异性，但用凋亡细胞处理小鼠后，这些抗体的量大幅增加。此外，PC和MDA抗体的相对量受VH基因遗传的影响。抗体与凋亡细胞的相互作用还介导了C1q的募集，这增强了未成熟树突状细胞对凋亡细胞的吞噬作用。重要的是，针对PC和MDA的IgM抗体是决定血清依赖性凋亡细胞吞噬效率的主要因素。因此，我们证明了一种机制，通过该机制，在未免疫小鼠中以及因免疫暴露于凋亡细胞而诱导产生的某些识别凋亡细胞上新抗原的天然抗体，能够增强未成熟树突状细胞吞噬凋亡细胞的功能能力。
Natural Abs, which arise without known immune exposure, have been described that specifically recognize cells dying from apoptosis, but their role in innate immunity remains poorly understood. Herein, we show that the immune response to neoantigenic determinants on apoptotic thymocytes is dominated by Abs to oxidation-associated Ags, phosphorylcholine (PC), a head group that becomes exposed during programmed cell death, and malondialdehyde (MDA), a reactive aldehyde degradation product of polyunsaturated lipids produced following exposure to reactive oxidation species. While natural Abs to apoptotic cells in naive adult mice were dominated by PC and MDA specificities, the amounts of these Abs were substantially boosted by treatment of mice with apoptotic cells. Moreover, the relative amounts of PC and MDA Abs was affected by VH gene inheritance. Ab interactions with apoptotic cells also mediated the recruitment of C1q, which enhanced apoptotic cell phagocytosis by immature dendritic cells. Significantly, IgM Abs to both PC and MDA were primary factors in determining the efficiency of serum-dependent apoptotic cell phagocytosis. Hence, we demonstrate a mechanism by which certain natural Abs that recognize neoantigens on apoptotic cells, in naive mice and those induced by immune exposure to apoptotic cells, can enhance the functional capabilities of immature dendritic cells for phagocytic engulfment of apoptotic cells.
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DOI：
10.1084/jem.172.1.371
发表时间：
1990-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Carmack CE;Shinton SA;Hayakawa K;Hardy RR
通讯作者：
Hardy RR
影响因子：
11.4
作者：
CHEN, C;ROBERTS, VA;RITTENBERG, MB
通讯作者：
RITTENBERG, MB
DOI：
10.1084/jem.20031763
发表时间：
2004-12-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chang MK;Binder CJ;Miller YI;Subbanagounder G;Silverman GJ;Berliner JA;Witztum JL
通讯作者：
Witztum JL
影响因子：
4.4
作者：
Ferguson, TA;Herndon, J;Green, DR
通讯作者：
Green, DR
影响因子：
15.9
作者：
EZEKOWITZ, RAB;SIM, RB;GORDON, S
通讯作者：
GORDON, S