CD36 and LC3B initiated autophagy in B cells regulates the humoral immune response.

CD36 and LC3B initiated autophagy in B cells regulates the humoral immune response.
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DOI:
10.1080/15548627.2021.1885183
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发表时间:
2021-11
期刊:
影响因子:
13.3
通讯作者:
Karlsson MCI
Karlsson MCI
中科院分区:
生物学1区
文献类型:
--
作者:
He C;Wang S;Zhou C;He M;Wang J;Ladds M;Lianoudaki D;Sedimbi SK;Lane DP;Westerberg LS;Li S;Karlsson MCI

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清道夫受体是模式识别受体,其识别外来配体和自身配体,并且通常作为共受体启动不同的细胞活化机制。清道夫受体CD 36在免疫系统中的功能主要在巨噬细胞中研究,但它也由先天性B型细胞高度表达,其中其功能较少被探索。在这里,我们报告说,CD 36参与大自噬/自噬在B细胞,在它的情况下,体液免疫反应受损。我们发现,CD 36缺陷型B细胞表现出浆细胞形成、增殖、线粒体动员和氧化磷酸化显著减少。这些变化伴随着自噬启动受损,我们发现CD 36调节自噬并与自噬体膜蛋白MAP 1 LC 3/LC 3(微管相关蛋白1轻链3)共定位。当我们研究T细胞依赖性免疫反应时,我们发现CD 36缺乏的小鼠,特别是B细胞,表现出减弱的生发中心反应,类别转换,抗体产生以及自噬体形成。这些发现确立了CD 36在B细胞应答中的关键作用,并且也可能有助于我们理解CD 36介导的其他细胞中的自噬以及已显示表达受体的B细胞淋巴瘤。缩略语:AICDA/AID:激活诱导的胞苷脱氨酶; ATG 5:自噬相关5; ATP:三磷酸腺苷; BCR:B细胞受体; CPG:未甲基化胞嘧啶-鸟苷; CQ:氯喹; DC:树突细胞; FO B:滤泡B细胞; GC:生发中心; IG:免疫球蛋白; LPS:脂多糖; MAP 1 LC 3/LC 3:微管相关蛋白1轻链3; MFI:平均荧光强度; MZ B:边缘区B细胞; NP-CGG:4-羟基-3-硝基苯乙酰-鸡丙种球蛋白; OCR:耗氧率; oxLDL:氧化低密度脂蛋白; PC:浆细胞; Rapa:雷帕霉素; SQSTM 1/p62:隔离体1; SRBC:绵羊红细胞; Tfh:滤泡辅助T细胞; TLR:toll样受体。
Scavenger receptors are pattern recognition receptors that recognize both foreign and self-ligands, and initiate different mechanisms of cellular activation, often as co-receptors. The function of scavenger receptor CD36 in the immune system has mostly been studied in macrophages but it is also highly expressed by innate type B cells where its function is less explored. Here we report that CD36 is involved in macro-autophagy/autophagy in B cells, and in its absence, the humoral immune response is impaired. We found that CD36-deficient B cells exhibit a significantly reduced plasma cell formation, proliferation, mitochondrial mobilization and oxidative phosphorylation. These changes were accompanied by impaired initiation of autophagy, and we found that CD36 regulated autophagy and colocalized with autophagosome membrane protein MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3). When we investigated T-cell-dependent immune responses, we found that mice with CD36 deficiency, specifically in B cells, exhibited attenuated germinal center responses, class switching, and antibody production as well as autophagosome formation. These findings establish a critical role for CD36 in B cell responses and may also contribute to our understanding of CD36-mediated autophagy in other cells as well as in B cell lymphomas that have been shown to express the receptor. Abbreviations: AICDA/AID: activation-induced cytidine deaminase; ATG5: autophagy related 5; ATP: adenosine triphosphate; BCR: B-cell receptor; CPG: unmethylated cytosine-guanosine; CQ: chloroquine; DC: dendritic cells; FOB: follicular B cells; GC: germinal center; Ig: immunoglobulin; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MFI: mean fluorescence intensity; MZB: marginal zone B cells; NP-CGG: 4-hydroxy-3-nitrophenylacetyl-chicken gamma globulin; OCR: oxygen consumption rate; oxLDL: oxidized low-density lipoprotein; PC: plasma cells; Rapa: rapamycin; SQSTM1/p62: sequestosome 1; SRBC: sheep red blood cells; Tfh: follicular helper T cells; TLR: toll-like receptor.
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发表时间: 2015-04-10
影响因子: 16.6
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期刊: Science signaling
影响因子: 7.3
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影响因子: 30.5
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