title: A mouse variable gene fragment binds to DNA independently of the BCR context: a possible role for immature B-cell repertoire establishment.
abstract: B-cell maturation occurs in several steps and requires constant stimulus for its continuing development. From the emergence of the pre-B-cell receptor, signal transduction stimulates and supports B-cell development. Current viewpoints indicate that both positive selection pressure for autoantigens and tonic signaling constitutively stimulate B-cell maturation. In this work, we tested for the presence of a putative DNA binding site in a variable gene segment in a germline configuration, independently of VDJ recombination. After a survey of the public antibody databases, we chose a single mouse heavy variable gene segment that is highly represented in anti-nucleic acid antibodies and tested it for ssDNA binding. A phage display approach was used to search for intrinsic binding to oligo deoxythymidine. The results revealed that binding to an antigen can be influenced by the use of a specific DNA binding V[Formula: see text] gene segment. Our data support the idea that some variable genes have intrinsic reactivity towards specific types of endogenous autoantigens, and this property may contribute to the establishment of the immature B-cell repertoire.
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Biologia, Universidade de Brasília, Brasília, Distrito Federal, Brazil.
authors.forename: Andrea Queiroz
authors.initials: AQ
authors.lastname: Maranhão
authors.forename: Maria Beatriz Walter
authors.initials: MB
authors.lastname: Costa
authors.forename: Leonardo
authors.initials: L
authors.lastname: Guedes
authors.forename: Pedro Manoel
authors.initials: PM
authors.lastname: Moraes-Vieira
authors.forename: Tainá
authors.initials: T
authors.lastname: Raiol
authors.forename: Marcelo Macedo
authors.initials: MM
authors.lastname: Brigido
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001665:Binding Sites; D004247:DNA / Q000276:immunology*; D051379:Mice
chemical_list: D000974:Antibodies, Antinuclear; D001324:Autoantigens; D004247:DNA
references.citation: Curr Protein Pept Sci. 2000 Sep;1(2):155-69
references.pmid: 12369915
references.citation: Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2262-7
references.pmid: 10051629
references.citation: J Immunol. 2006 Apr 1;176(7):4221-34
references.pmid: 16547259
references.citation: Nat Rev Immunol. 2006 Apr;6(4):283-94
references.pmid: 16557260
references.citation: J Immunol. 2004 Oct 1;173(7):4265-71
references.pmid: 15383554
references.citation: PLoS One. 2012;7(8):e41469
references.pmid: 22870226
references.citation: PLoS Biol. 2005 Mar;3(3):e82
references.pmid: 15752064
references.citation: Mol Immunol. 2007 Jan;44(4):412-22
references.pmid: 16581131
references.citation: Mol Immunol. 2007 Mar;44(8):1914-21
references.pmid: 17084454
references.citation: Nat Rev Immunol. 2010 Aug;10(8):543-53
references.pmid: 20651744
references.citation: Nucleic Acids Res. 2010 Jul;38(13):e142
references.pmid: 20460461
references.citation: J Immunol. 1991 Mar 15;146(6):2005-9
references.pmid: 1900879
references.citation: BMC Genomics. 2012 Jan 25;13:43
references.pmid: 22276739
references.citation: J Biol Chem. 2004 Apr 2;279(14):13418-24
references.pmid: 14668327
references.citation: J Mol Graph. 1996 Feb;14(1):33-8, 27-8
references.pmid: 8744570
references.citation: J Immunol. 2001 Oct 1;167(7):3746-55
references.pmid: 11564791
references.citation: Protein Eng Des Sel. 2009 Jan;22(1):9-18
references.pmid: 18988692
references.citation: Cell. 2004 Jun 11;117(6):787-800
references.pmid: 15186779
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3497-500
references.pmid: 12824352
references.citation: Proteins. 1991;11(3):159-75
references.pmid: 1749770
references.citation: Curr Opin Immunol. 2012 Apr;24(2):166-72
references.pmid: 22398125
references.citation: Science. 2003 Sep 5;301(5638):1374-7
references.pmid: 12920303
references.citation: Cell Mol Life Sci. 2003 Feb;60(2):309-20
references.pmid: 12678496
references.citation: Mol Immunol. 2009 Oct;46(16):3420-6
references.pmid: 19699528
references.citation: Immunity. 2008 Dec 19;29(6):912-21
references.pmid: 19084434
references.citation: Genome Res. 2004 Jun;14(6):1188-90
references.pmid: 15173120
references.citation: J Exp Med. 1997 Nov 3;186(9):1513-22
references.pmid: 9348309
references.citation: Nat Immunol. 2004 Jun;5(6):645-50
references.pmid: 15156139
references.citation: Braz J Med Biol Res. 2000 May;33(5):569-79
references.pmid: 10775889
references.citation: J Exp Med. 2010 Mar 15;207(3):607-21
references.pmid: 20176802
references.citation: J Mol Biol. 1990 Oct 5;215(3):403-10
references.pmid: 2231712
references.citation: Nature. 2012 Sep 6;489(7414):160-4
references.pmid: 22902503
references.citation: Immunol Rev. 2000 Aug;176:10-8
references.pmid: 11043764