NFκB induces overexpression of bovine FcRn: A novel mechanism that further contributes to the enhanced immune response in genetically modified animals carrying extra copies of FcRn

mAbs

Volumn 5, Issue 6, 2013, Pages 860-871

  Cervenak, Judit ^a   Doleschall, Márton ^b   Bender, Balázs ^a   Mayer, Balázs ^b   Schneider, Zita ^c   Doleschall, Zoltán ^d   Zhao, Yaofeng ^e   Bosze, Zsuzsanna ^f   Hammarström, Lennart ^g   Oster, Wolfgang ^a   Kacskovics, Imre ^a,c  

^a ImmunoGenes Kft ^*  (Hungary)

^b SEMMELWEIS UNIVERSITY   (Hungary)

^c EÖTVÖS LORÁND UNIVERSITY   (Hungary)

^d NATIONAL INSTITUTE OF ONCOLOGY   (Hungary)

^e CHINA AGRICULTURAL UNIVERSITY   (China)

^f SZENT ISTVÁN UNIVERSITY   (Hungary)

^g KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

Antigen presentation; FcRn; Humoral; IgG; Immune response; NF B; Transgenic mouse

Indexed keywords

ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; FC RECEPTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LIPOPOLYSACCHARIDE; TOLL LIKE RECEPTOR 4; FC RECEPTOR, NEONATAL; HLA ANTIGEN CLASS 1; IMMUNOLOGICAL ADJUVANT;

ANIMAL CELL; ARTICLE; CELL ISOLATION; CONTROLLED STUDY; ENDOTHELIUM CELL; FLOW CYTOMETRY; GEL MOBILITY SHIFT ASSAY; GENE INDUCTION; GENE OVEREXPRESSION; HUMORAL IMMUNITY; MOUSE; NONHUMAN; NORTHERN BLOTTING; PERITONEUM MACROPHAGE; PROMOTER REGION; RECEPTOR UPREGULATION; REPORTER GENE; TRANSGENIC ANIMAL; ANIMAL; BINDING SITE; BOVINAE; CELL LINE; DRUG EFFECTS; GENE EXPRESSION; GENETICS; HUMAN; IMMUNOLOGY; METABOLISM; SPLEEN;

ADJUVANTS, IMMUNOLOGIC; ANIMALS; ANIMALS, GENETICALLY MODIFIED; BINDING SITES; CATTLE; CELL LINE; ENDOTHELIAL CELLS; GENE EXPRESSION; HISTOCOMPATIBILITY ANTIGENS CLASS I; HUMANS; LIPOPOLYSACCHARIDES; MICE; NF-KAPPA B; PROMOTER REGIONS, GENETIC; RECEPTORS, FC; SPLEEN;

EID: 84889856808     PISSN: 19420862     EISSN: 19420870     Source Type: Journal    
DOI: 10.4161/mabs.26507     Document Type: Article

References (57)

1. Brambell FWR, Halliday R, Morris IG. Interference by human and bovine serum and serum protein fractions with the absorption of antibodies by suckling rats and mice. Proc R Soc Lond B Biol Sci 1958; 149:1-11; PMID:13554426; http://dx.doi.org/10.1098/rspb.1958.0046
2. Brambell FWR, Hemmings WA, Morris IG. A theoretical model of gammaglobulin catabolism. Nature 1964; 203:1352-4; PMID:14207307; http://dx.doi.org/10.1038/2031352a0
3. Jones EA, Waldmann TA. The mechanism of intestinal uptake and transcellular transport of IgG in the neonatal rat. J Clin Invest 1972; 51:2916-27; PMID:5080417; http://dx.doi.org/10.1172/JCI107116
4. Rodewald R, Kraehenbuhl JP. Receptor-mediated transport of IgG. J Cell Biol 1984; 99:159s-64s; PMID:6235233; http://dx.doi.org/10.1083/jcb.99.1.159s
5. Simister NE, Rees AR. Isolation and characterization of an Fc receptor from neonatal rat small intestine. Eur J Immunol 1985; 15:733-8; PMID:2988974; http://dx.doi.org/10.1002/eji.1830150718
6. West AP Jr., Bjorkman PJ. Crystal structure and immunoglobulin G binding properties of the human major histocompatibility complex-related Fc receptor(,). Biochemistry 2000; 39:9698-708; PMID:10933786; http://dx.doi.org/10.1021/ bi000749m
7. Simister NE, Mostov KE. An Fc receptor structurally related to MHC class I antigens. Nature 1989; 337:184-7; PMID:2911353; http://dx.doi.org/10.1038/ 337184a0
8. Borvak J, Richardson J, Medesan C, Antohe F, Radu C, Simionescu M, Ghetie V, Ward ES. Functional expression of the MHC class I-related receptor, FcRn, in endothelial cells of mice. Int Immunol 1998; 10:1289-98; PMID:9786428; http://dx.doi.org/10.1093/intimm/10.9.1289
9. Zhu X, Meng G, Dickinson BL, Li X, Mizoguchi E, Miao L, Wang Y, Robert C, Wu B, Smith PD, et al. MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells. J Immunol 2001; 166:3266-76; PMID:11207281
10. Akilesh S, Christianson GJ, Roopenian DC, Shaw AS. Neonatal FcR expression in bone marrow-derived cells functions to protect serum IgG from catabolism. J Immunol 2007; 179:4580-8; PMID:17878355
11. Montoyo HP, Vaccaro C, Hafner M, Ober RJ, Mueller W, Ward ES. Conditional deletion of the MHC class I-related receptor FcRn reveals the sites of IgG homeostasis in mice. Proc Natl Acad Sci U S A 2009; 106:2788-93; PMID:19188594; http://dx.doi.org/10.1073/pnas.0810796106
12. Ward ES, Ober RJ. Chapter 4: Multitasking by exploitation of intracellular transport functions the many faces of FcRn. Adv Immunol 2009; 103:77-115; PMID:19755184; http://dx.doi.org/10.1016/S0065-2776(09)03004-1
13. Roopenian DC, Sun VZ. Clinical ramifications of the MHC family Fc receptor FcRn. J Clin Immunol 2010; 30:790-7; PMID:20848168; http://dx.doi.org/10.1007/s10875-010-9458-6
14. Kuo TT, Baker K, Yoshida M, Qiao SW, Aveson VG, Lencer WI, Blumberg RS. Neonatal Fc receptor: from immunity to therapeutics. J Clin Immunol 2010; 30:777-89; PMID:20886282; http://dx.doi.org/10.1007/s10875-010-9468-4
15. Vidarsson G, Stemerding AM, Stapleton NM, Spliethoff SE, Janssen H, Rebers FE, de Haas M, van de Winkel JG. FcRn: an IgG receptor on phagocytes with a novel role in phagocytosis. Blood 2006; 108:3573-9; PMID:16849638; http://dx.doi.org/10.1182/blood-2006-05-024539
16. Qiao SW, Kobayashi K, Johansen FE, Sollid LM, Andersen JT, Milford E, Roopenian DC, Lencer WI, Blumberg RS. Dependence of antibody-mediated presentation of antigen on FcRn. Proc Natl Acad Sci U S A 2008; 105:9337-42; PMID:18599440; http://dx.doi.org/10.1073/pnas.0801717105
17. Mi W, Wanjie S, Lo ST, Gan Z, Pickl-Herk B, Ober RJ, Ward ES. Targeting the neonatal fc receptor for antigen delivery using engineered fc fragments. J Immunol 2008; 181:7550-61; PMID:19017944
18. Liu X, Lu L, Yang Z, Palaniyandi S, Zeng R, Gao LY, Mosser DM, Roopenian DC, Zhu X. The neonatal FcR-mediated presentation of immune-complexed antigen is associated with endosomal and phagosomal pH and antigen stability in macrophages and dendritic cells. J Immunol 2011; 186:4674-86; PMID:21402891; http://dx.doi.org/10.4049/jimmunol.1003584
19. Baker K, Qiao SW, Kuo TT, Aveson VG, Platzer B, Andersen JT, Sandlie I, Chen Z, de Haar C, Lencer WI, et al. Neonatal Fc receptor for IgG (FcRn) regulates cross-presentation of IgG immune complexes by CD8-CD11b+ dendritic cells. Proc Natl Acad Sci U S A 2011; 108:9927-32; PMID:21628593; http://dx.doi.org/10.1073/pnas.1019037108
20. Baranyi M, Cervenak J, Bender B, Kacskovics I. Transgenic rabbits that overexpress the neonatal Fc receptor (FcRn) generate higher quantities and improved qualities of anti-thymocyte globulin (ATG). PLoS ONE 2013; Forthcoming 2013.
21. Végh A, Farkas A, Kövesdi D, Papp K, Cervenak J, Schneider Z, Bender B, Hiripi L, László G, Prechl J, et al. FcRn overexpression in transgenic mice results in augmented APC activity and robust immune response with increased diversity of induced antibodies. PLoS One 2012; 7:e36286; PMID:22558422; http://dx.doi.org/10.1371/journal.pone.0036286
22. Catunda Lemos AP, Cervenak J, Bender B, Hoffmann OI, Baranyi M, Kerekes A, Farkas A, Bosze Z, Hiripi L, Kacskovics I. Characterization of the rabbit neonatal Fc receptor (FcRn) and analyzing the immunophenotype of the transgenic rabbits that overexpresses FcRn. PLoS One 2012; 7:e28869; PMID:22247762; http://dx.doi.org/10.1371/journal.pone.0028869
23. Végh A, Cervenak J, Jankovics I, Kacskovics I. FcRn overexpression in mice results in potent humoral response against weakly immunogenic antigen. MAbs 2011; 3:173-80; PMID:21239891; http://dx.doi.org/10.4161/mabs.3.2.14462
24. Schneider Z, Cervenak J, Baranyi M, Papp K, Prechl J, László G, Erdei A, Kacskovics I. Transgenic expression of bovine neonatal Fc receptor in mice boosts immune response and improves hybridoma production efficiency without any sign of autoimmunity. Immunol Lett 2011; 137:62-9; PMID:21338624; http://dx.doi.org/10.1016/j.imlet.2011.02.018
25. Cervenak J, Bender B, Schneider Z, Magna M, Carstea BV, Liliom K, Erdei A, Bosze Z, Kacskovics I. Neonatal FcR overexpression boosts humoral immune response in transgenic mice. J Immunol 2011; 186:959-68; PMID:21148035; http://dx.doi.org/10.4049/jimmunol.1000353
26. Kacskovics I, Cervenak J, Erdei A, Goldsby RA, Butler JE. Recent advances using FcRn overexpression in transgenic animals to overcome impediments of standard antibody technologies to improve the generation of specific antibodies. MAbs 2011; 3:431-9; PMID:22048692; http://dx.doi.org/10.4161/mabs.3.5.17023
27. Doleschall M, Zhao Y, Mayer B, Hammarström L, Kacskovics I. Isolation of the gene encoding the bovine neonatal Fc receptor. Vet Immunol Immunopathol 2005; 108:145-50; PMID:16095719; http://dx.doi.org/10.1016/j. vetimm.2005.07.007
28. Liu X, Ye L, Christianson GJ, Yang JQ, Roopenian DC, Zhu XNF. NF-kappaB signaling regulates functional expression of the MHC class I-related neonatal Fc receptor for IgG via intronic binding sequences. J Immunol 2007; 179:2999-3011; PMID:17709515
29. Li Q, Verma IM. NF-kappaB regulation in the immune system. Nat Rev Immunol 2002; 2:725-34; PMID:12360211; http://dx.doi.org/10.1038/nri910
30. Ulevitch RJ. Therapeutics targeting the innate immune system. Nat Rev Immunol 2004; 4:512-20; PMID:15229470; http://dx.doi.org/10.1038/nri1396
31. Bender B, Bodrogi L, Mayer B, Schneider Z, Zhao Y, Hammarström L, Eggen A, Kacskovics I, Bosze Z. Position independent and copy-number-related expression of the bovine neonatal Fc receptor alpha-chain in transgenic mice carrying a 102 kb BAC genomic fragment. Transgenic Res 2007; 16:613-27; PMID:17594529; http://dx.doi.org/10.1007/s11248-007-9108-9
32. Gilmore TD. Introduction to NF-kappaB: players, pathways, perspectives. Oncogene 2006; 25:6680-4; PMID:17072321; http://dx.doi.org/10.1038/sj.onc. 1209954
33. Van Kampen C, Mallard BA. Regulation of bovine E-selectin expression by recombinant tumor necrosis factor alpha and lipopolysaccharide. Vet Immunol Immunopathol 2001; 79:151-65; PMID:11389952; http://dx.doi.org/10.1016/S0165- 2427(01)00249-5
34. Wang J, Ando T, Dunn AJ. Effect of homologous interleukin-1, interleukin-6 and tumor necrosis factor-alpha on the core body temperature of mice. Neuroimmunomodulation 1997; 4:230-6; PMID:9650815
35. Dickinson BL, Badizadegan K, Wu Z, Ahouse JC, Zhu X, Simister NE, Blumberg RS, Lencer WI. Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line. J Clin Invest 1999; 104:903-11; PMID:10510331; http://dx.doi.org/10.1172/JCI6968
36. Jiang L, Wang J, Solorzano-Vargas RS, Tsai HV, Gutierrez EM, Ontiveros LO, Kiela PR, Wu SV, Martín MG. Characterization of the rat intestinal Fc receptor (FcRn) promoter: transcriptional regulation of FcRn gene by the Sp family of transcription factors. Am J Physiol Gastrointest Liver Physiol 2004; 286:G922-31; PMID:15132949; http://dx.doi.org/10.1152/ajpgi.00131.2003
37. Kandil E, Noguchi M, Ishibashi T, Kasahara M. Structural and phylogenetic analysis of the MHC class I-like Fc receptor gene. J Immunol 1995; 154:5907-18; PMID:7538537
38. Tiwari B, Junghans RP. Functional analysis of the mouse Fcgrt 5' proximal promoter. Biochim Biophys Acta 2005; 1681:88-98; PMID:15627500; http://dx.doi.org/10.1016/j.bbaexp.2004.10.002
39. Liu X, Ye L, Bai Y, Mojidi H, Simister NE, Zhu X. Activation of the JAK/STAT-1 signaling pathway by IFN-gamma can down-regulate functional expression of the MHC class I-related neonatal Fc receptor for IgG. J Immunol 2008; 181:449-63; PMID:18566411
40. Schug J, Overton GC. TESS: Transcription Element Search System on the WWW. Philadelphia (PA): Computational Biology and Informatics Laboratory, School of Medicine, University of Pennsylvania; 1997.
41. Heinemeyer T, Wingender E, Reuter I, Hermjakob H, Kel AE, Kel OV, Ignatieva EV, Ananko EA, Podkolodnaya OA, Kolpakov FA, et al. Databases on transcriptional regulation: TRANSFAC, TRRD and COMPEL. Nucleic Acids Res 1998; 26:362-7; PMID:9399875; http://dx.doi.org/10.1093/nar/26.1.362
42. Doleschall M, Mayer B, Cervenak J, Cervenak L, Kacskovics I. Cloning, expression and characterization of the bovine p65 subunit of NFkappaB. Dev Comp Immunol 2007; 31:945-61; PMID:17306370; http://dx.doi.org/10.1016/j.dci.2006.12. 007
43. Petkova SB, Akilesh S, Sproule TJ, Christianson GJ, Al Khabbaz H, Brown AC, Presta LG, Meng YG, Roopenian DC. Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease. Int Immunol 2006; 18:1759-69; PMID:17077181; http://dx.doi.org/10.1093/intimm/dxl110
44. Antohe F, Rǎ;dulescu L, Gafencu A, Ghetie V, Simionescu M. Expression of functionally active FcRn and the differentiated bidirectional transport of IgG in human placental endothelial cells. Hum Immunol 2001; 62:93-105; PMID:11182218; http://dx.doi.org/10.1016/S0198-8859(00)00244-5
45. Borregaard N, Kjeldsen L, Sengeløv H, Diamond MS, Springer TA, Anderson HC, Kishimoto TK, Bainton DF. Changes in subcellular localization and surface expression of L-selectin, alkaline phosphatase, and Mac-1 in human neutrophils during stimulation with inflammatory mediators. J Leukoc Biol 1994; 56:80-7; PMID:7517990
46. Ghosn EE, Cassado AA, Govoni GR, Fukuhara T, Yang Y, Monack DM, Bortoluci KR, Almeida SR, Herzenberg LA, Herzenberg LA. Two physically, functionally, and developmentally distinct peritoneal macrophage subsets. Proc Natl Acad Sci U S A 2010; 107:2568-73; PMID:20133793; http://dx.doi.org/10.1073/pnas.0915000107
47. Zhu X, Peng J, Raychowdhury R, Nakajima A, Lencer WI, Blumberg RS. The heavy chain of neonatal Fc receptor for IgG is sequestered in endoplasmic reticulum by forming oligomers in the absence of beta2-microglobulin association. Biochem J 2002; 367:703-14; PMID:12162790; http://dx.doi.org/10. 1042/BJ20020200
48. Gobin SJ, Biesta P, Van den Elsen PJ. Regulation of human beta 2-microglobulin transactivation in hematopoietic cells. Blood 2003; 101:3058-64; PMID:12480693; http://dx.doi.org/10.1182/blood-2002-09-2924
49. Lonergan M, Dey A, Becker KG, Drew PD, Ozato K. A regulatory element in the beta 2-microglobulin promoter identified by in vivo footprinting. Mol Cell Biol 1993; 13:6629-39; PMID:8413259
50. Geymayer S, Doppler W. Activation of NF-kappaB p50/p65 is regulated in the developing mammary gland and inhibits STAT5-mediated beta-casein gene expression. FASEB J 2000; 14:1159-70; PMID:10834938
51. Schug J, Overton GC. Modeling transcription factor binding sites with Gibbs Sampling and Minimum Description Length encoding. Proceedings / International Conference on Intelligent Systems for Molecular Biology; ISMB 1997; 5:268-71.
52. Wingender E, Chen X, Fricke E, Geffers R, Hehl R, Liebich I, Krull M, Matys V, Michael H, Ohnhäuser R, et al. The TRANSFAC system on gene expression regulation. Nucleic Acids Res 2001; 29:281-3; PMID:11125113; http://dx.doi.org/10.1093/nar/29.1.281
53. Gustin K, Burk RD. PCR-directed linker scanning mutagenesis. Methods Mol Biol 2000; 130:85-90; PMID:10589423
54. Boussif O, Lezoualc'h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc Natl Acad Sci U S A 1995; 92:7297-301; PMID:7638184; http://dx.doi.org/10.1073/pnas.92.16.7297
55. Wolff B, Naumann M. INK4 cell cycle inhibitors direct transcriptional inactivation of NF-kappaB. Oncogene 1999; 18:2663-6; PMID:10353611; http://dx.doi.org/10.1038/sj.onc.1202617
56. Zeöld A, Doleschall M, Haffner MC, Capelo LP, Menyhért J, Liposits Z, da Silva WS, Bianco AC, Kacskovics I, Fekete C, et al. Characterization of the nuclear factor-kappa B responsiveness of the human dio2 gene. Endocrinology 2006; 147:4419-29; PMID:16728495; http://dx.doi.org/10.1210/ en.2005-1608
57. Kacskovics I, Kis Z, Mayer B, West AP Jr., Tiangco NE, Tilahun M, Cervenak L, Bjorkman PJ, Goldsby RA, Szenci O, et al. FcRn mediates elongated serum half-life of human IgG in cattle. Int Immunol 2006; 18:525-36; PMID:16481343; http://dx.doi.org/10.1093/intimm/dxh393