FcRn overexpression in mice results in potent humoral response against weakly immunogenic antigen.
The neonatal Fc receptor (FcRn) regulates IgG and albumin homeostasis, mediates maternal IgG transport, is active in phagocytosis and delivers antigen for presentation. We have previously shown that transgenic (tg) mice that have been created to overexpress bovine FcRn (bFcRn) demonstrate increased half-life of mouse IgG, significantly increased antigen-specific IgG in serum and augmented expansion of antigen-specific B cells and plasma cells after immunization. One of the interesting questions surrounding this enhanced immune response is whether these tg mice could effectively induce immune response to weakly immunogenic antigens. To address this question, we immunized these bFcRn tg mice with a conserved hemagglutinin subunit 2 (HA2)-based synthetic peptide that was recently found to be effectively targeted by neutralizing antibodies. Using an ELISA system, we found that, whereas wild-type mice showed a weak immune response and developed only a de minimis amount of antibody against the epitope, FcRn over-expressing animals mounted a robust reaction expressed in specific antibody titers on day 28 that continued to rise through day 50. Consistent with our previous data, the enhanced immune response resulting from the FcRn overexpression was also associated with a substantial increase in the number of spleen derived B cells, dendritic cells, granulocytes and plasma cells. Based on this evidence, we propose that tg mice that overexpress bFcRn offer major advantages in monoclonal antibody production because the tg mice would allow the generation of antibodies (hybridomas) to weakly immunogenic antigens that otherwise would be difficult or even impossible to make.
ImmunoGenes Ltd., Budakeszi, Hungary.
Attila
A
Végh
Judit
J
Cervenak
István
I
Jankovics
Imre
I
Kacskovics
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D000917:Antibody Formation; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D002417:Cattle; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008958:Models, Molecular; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D011961:Receptors, Fc / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D000914:Antibodies, Viral; D000941:Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D011961:Receptors, Fc; C483468:hemagglutinin, human influenza A virus; C100688:Fc receptor, neonatal
Curr Opin Immunol. 1996 Dec;8(6):852-9
8994866
Nature. 1975 Aug 7;256(5517):495-7
1172191
Science. 2009 Apr 10;324(5924):246-51
19251591
Immunology. 1981 Jun;43(2):371-8
7019054
Nature. 1996 Jan 25;379(6563):346-9
8552190
J Immunol. 2011 Jan 15;186(2):959-68
21148035
Adv Immunol. 2009;103:77-115
19755184
J Immunol. 2010 Jun 1;184(11):6293-8
20439912
Nucleic Acids Res. 2003 Jan 1;31(1):474-7
12520055
Proc Natl Acad Sci U S A. 2008 Jul 8;105(27):9337-42
18599440
Immunome Res. 2006 Apr 24;2:2
16635264
PLoS Curr. 2010 Mar 22;2:RRN1152
20352039
PLoS One. 2008;3(12):e3942
19079604
Hybridoma. 1996 Oct;15(5):365-71
8913786
J Clin Microbiol. 1980 Sep;12(3):426-32
6260835
J Immunol. 2007 Sep 1;179(5):2999-3011
17709515
Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18979-84
20956293
J Immunol. 2008 Dec 1;181(11):7550-61
19017944
Nat Struct Mol Biol. 2009 Mar;16(3):265-73
19234466
J Exp Med. 2010 Nov 22;207(12):2767-78
21078890
J Exp Med. 2002 May 6;195(9):1167-74
11994421
Curr Opin Mol Ther. 2005 Apr;7(2):157-63
15844624
Transgenic Res. 2007 Oct;16(5):613-27
17594529
J Immunol. 2001 Mar 1;166(5):3266-76
11207281
Blood. 2006 Nov 1;108(9):3094-102
16835380
Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8661-5
1924327
Eur J Immunol. 1985 Aug;15(8):793-8
4029257
Nucleic Acids Res. 2007 Jan;35(Database issue):D298-300
17135201
J Immunol. 2000 Dec 15;165(12):6738-42
11120792
J Immunol. 1971 Sep;107(3):822-31
5106411
Nature. 1992 Mar 26;356(6367):314-7
1372394
FEBS Lett. 1990 Dec 10;276(1-2):172-4
1702393
ILAR J. 2005;46(3):314-9
15953839