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Preisendörfer, S. ; Ishikawa, Y.* ; Hennen, E. ; Winklmeier, S.* ; Schupp, J.C.* ; Knüppel, L. ; Fernandez, I.E. ; Binzenhöfer, L. ; Flatley, A. ; Juan-Guardela, B.M.* ; Ruppert, C.* ; Guenther, A.* ; Frankenberger, M. ; Hatz, R.A.* ; Kneidinger, N.* ; Behr, J.* ; Feederle, R. ; Schepers, A. ; Hilgendorff, A. ; Kaminski, N.* ; Meinl, E.* ; Bächinger, H.P.* ; Eickelberg, O. ; Staab-Weijnitz, C.A.

FK506-binding protein 11 is a novel plasma cell-specific antibody folding catalyst with increased expression in idiopathic pulmonary fibrosis.

Cells 11:1341 (2022)

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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 antibodyproducing 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 stressmediated 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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Antibody Folding ; Er Stress ; Fk506-binding Protein ; Immunophilin ; Interstitial Lung Disease ; Lung Fibrosis ; Peptidyl-prolyl Isomerase ; Tacrolimus

ISSN (print) / ISBN 2073-4409

e-ISSN 2073-4409

Journal Cells

Quellenangaben Volume: 11, Issue: 8, Article Number: 1341

Publisher MDPI

Publishing Place Basel

Non-patent literature Publications

Institute(s) Lung Health and Immunity (LHI)
CF Monoclonal Antibodies (CF-MAB)

Grants the Helmholtz Association, the German Center for Lung Research (DZL), the Deutsche Forschungsgemeinschaft (DFG) within the Research Training Group
Shriners Hospital for Children
The CPC Research School
Deutsche Forschungsgemeinschaft
NIH HHS