FK506-Binding Protein 11 Is a Novel Plasma Cell-Specific Antibody Folding Catalyst with Increased Expression in Idiopathic Pulmonary Fibrosis.
FK506-Binding Protein 11 Is a Novel Plasma Cell-Specific Antibody Folding Catalyst with Increased Expression in Idiopathic Pulmonary Fibrosis.
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FK506结合蛋白11是一种新型的浆细胞特异性抗体折叠催化剂，在特发性肺纤维化中的表达增加。
DOI：
10.3390/cells11081341
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发表时间：
2022-04-14
期刊：
影响因子：
6
通讯作者：
Staab-Weijnitz, Claudia A.
中科院分区：
文献类型：
--
作者：
Preisendoerfer, Stefan;Ishikawa, Yoshihiro;Hennen, Elisabeth;Winklmeier, Stephan;Schupp, Jonas C.;Knueppel, Larissa;Fernandez, Isis E.;Binzenhofer, Leonhard;Flatley, Andrew;Juan-Guardela, Brenda M.;Ruppert, Clemens;Guenther, Andreas;Frankenberger, Marion;Hatz, Rudolf A.;Kneidinger, Nikolaus;Behr, Jurgen;Feederle, Regina;Schepers, Aloys;Hilgendorff, Anne;Kaminski, Naftali;Meinl, Edgar;Baechinger, Hans Peter;Eickelberg, Oliver;Staab-Weijnitz, Claudia A.
关键词：
抗体是适应性免疫反应的中心效应者，是广泛使用的治疗方法，但也可能导致疾病的生物分子。抗体折叠催化剂在浆细胞中的定义不完全。特发性肺纤维化(IPF)是一种致命性慢性肺部疾病，其自身免疫特征日益为人们所认识。我们发现在IPF肺中FK506结合蛋白11(FKBP11)的表达增加，其中FKBP11特异性地定位于产生抗体的浆细胞。在淋巴组织中同样观察到浆细胞特异性的FKBP11的表达，在体外B细胞向浆细胞的分化伴随着FKBP11的表达诱导。重组人FKBP11能在体外折叠抗体，并被FK506抑制，强烈支持抗体肽-脯氨酰顺反异构酶的功能。内质网应激在细胞系中的诱导表现为FKBP11在未折叠蛋白反应的背景下以X盒结合蛋白1(XBP1)依赖的方式诱导。在肺泡上皮细胞系中，FKBP11基因缺失增加了对内质网应激所致细胞死亡的易感性，而在产生抗体的杂交瘤细胞系中，FKBP11基因敲除既不会导致细胞死亡，也不会减少免疫球蛋白抗体的表达或分泌。同样，同一杂交瘤细胞株的抗体分泌不受已建立的抗体肽-Pro异构酶亲环素B基因敲除的影响。结果与FKBP11作为一种新的XBP1调节的抗体肽基-脯氨基顺式-反式异构酶是一致的，并表明产生抗体的杂交瘤细胞的内质网驻留折叠机制存在显著冗余。
Antibodies are central effectors of the adaptive immune response, widespread used therapeutics, but also potentially disease-causing biomolecules. Antibody folding catalysts in the plasma cell are incompletely defined. Idiopathic pulmonary fibrosis (IPF) is a fatal chronic lung disease with increasingly recognized autoimmune features. We found elevated expression of FK506-binding protein 11 (FKBP11) in IPF lungs where FKBP11 specifically localized to antibody-producing plasma cells. Suggesting a general role in plasma cells, plasma cell-specific FKBP11 expression was equally observed in lymphatic tissues, and in vitro B cell to plasma cell differentiation was accompanied by induction of FKBP11 expression. Recombinant human FKBP11 was able to refold IgG antibody in vitro and inhibited by FK506, strongly supporting a function as antibody peptidyl-prolyl cis-trans isomerase. Induction of ER stress in cell lines demonstrated induction of FKBP11 in the context of the unfolded protein response in an X-box-binding protein 1 (XBP1)-dependent manner. While deficiency of FKBP11 increased susceptibility to ER stress-mediated cell death in an alveolar epithelial cell line, FKBP11 knockdown in an antibody-producing hybridoma cell line neither induced cell death nor decreased expression or secretion of IgG antibody. Similarly, antibody secretion by the same hybridoma cell line was not affected by knockdown of the established antibody peptidyl-prolyl isomerase cyclophilin B. The results are consistent with FKBP11 as a novel XBP1-regulated antibody peptidyl-prolyl cis-trans isomerase and indicate significant redundancy in the ER-resident folding machinery of antibody-producing hybridoma cells.
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影响因子：
16
作者：
Feige, Matthias J.;Groscurth, Sandra;Marcinowski, Moritz;Shimizu, Yuichiro;Kessler, Horst;Hendershot, Linda M.;Buchner, Johannes
通讯作者：
Buchner, Johannes
DOI：
10.1038/nrg2703
发表时间：
2010-01
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
DOI：
10.3324/haematol.2009.018689
发表时间：
2010-06-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Caraux, Anouk;Klein, Bernard;Perez-Andres, Martin
通讯作者：
Perez-Andres, Martin
DOI：
10.1165/rcmb.2013-0310oc
发表时间：
2015-02-01
影响因子：
6.4
作者：
Bauer, Yasmina;Tedrow, John;Kaminski, Naftali
通讯作者：
Kaminski, Naftali
影响因子：
16.6
作者：
Angelidis, Ilias;Simon, Lukas M.;Schiller, Herbert B.
通讯作者：
Schiller, Herbert B.