title: Molecular bases of genetic diversity and evolution of the immunoglobulin heavy chain variable region (IGHV) gene locus in leporids.
abstract: The rabbit has long been a model for studies of the immune system. Work using rabbits contributed both to the battle against infectious diseases such as rabies and syphilis, and to our knowledge, of antibodies' structure, function, and regulated expression. With the description of rabbit Ig allotypes, the discovery of different gene segments encoding immunoglobulins became possible. This challenged the "one gene-one protein" dogma. The observation that rabbit allotypic specificities of the variable regions were present on IgM and IgG molecules also led to the hypothesis of Ig class switching. Rabbit allotypes contributed to the documentation of phenomena such as allelic exclusion and imbalance in production of allelic gene products. During the last 30 years, the rabbit Ig allotypes revealed a number of unique features, setting them apart from mice, humans, and other mammals. Here, we review the most relevant findings concerning the rabbit IGHV. Among these are the preferential usage of one VH gene in VDJ rearrangements, the existence of trans-species polymorphism in the IGHV locus revealed by serology and confirmed by sequencing IGHV genes in Lepus, the unusually large genetic distances between allelic lineages and the fact that the antibody repertoire is diversified in this species only after birth. The whole genome sequence of a rabbit, plus re-sequencing of additional strains and related genera, will allow further evolutionary investigations of antibody variation. Continued research will help define the roles that genetic, allelic, and population diversity at antibody loci may play in host-parasite interactions.
authors: Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, 4485-661 Vairão, Portugal.
authors: Ana
authors: A
authors: Pinheiro
authors: Dennis
authors: D
authors: Lanning
authors: Paulo C
authors: PC
authors: Alves
authors: Rose G
authors: RG
authors: Mage
authors: Katherine L
authors: KL
authors: Knight
authors: Wessel
authors: W
authors: van der Loo
authors: Pedro J
authors: PJ
authors: Esteves
references: Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7799-806
references: 9223266
references: Mol Biol Evol. 1984 Feb;1(2):195-212
references: 6443795
references: Genetics. 1993 Sep;135(1):171-87
references: 8224818
references: Mol Immunol. 1982 Jul;19(7):841-6
references: 7121466
references: Eur J Immunogenet. 2002 Dec;29(6):529-35
references: 12437613
references: J Immunol. 1967 Mar;98(3):502-9
references: 4164057
references: Nat New Biol. 1971 Mar 10;230(10):63-4
references: 5279812
references: Eur J Immunol. 2000 Dec;30(12):3634-44
references: 11169406
references: Int J Immunogenet. 2006 Jun;33(3):171-7
references: 16712647
references: Immunochemistry. 1975 Mar;12(3):241-7
references: 811544
references: Adv Immunol. 1975;21:35-86
references: 50001
references: Immunogenetics. 1997;45(6):444-6
references: 9089105
references: Eur J Immunol. 1979 Sep;9(9):690-5
references: 92412
references: Eur J Immunol. 1978 May;8(5):315-24
references: 99318
references: Immunol Rev. 2000 Jun;175:214-28
references: 10933605
references: Proc Natl Acad Sci U S A. 1990 Jul;87(14):5444-8
references: 2115171
references: Eur J Immunol. 1990 Jun;20(6):1401-4
references: 1973389
references: J Immunol. 1977 Jul;119(1):287-94
references: 406325
references: J Immunol. 1979 Apr;122(4):1203-8
references: 376713
references: Immunogenetics. 1989;30(5):315-29
references: 2509340
references: Gene. 2004 Apr 14;330:49-59
references: 15087123
references: Mol Immunol. 1984 Nov;21(11):1067-81
references: 6083445
references: Mol Biol Evol. 2011 Jun;28(6):1801-16
references: 21216839
references: J Immunol. 1976 Nov;117(5 Pt 1):1567-72
references: 794414
references: Immunol Rev. 1982;67:73-85
references: 6751997
references: Proc Natl Acad Sci U S A. 1980 Apr;77(4):2158-62
references: 6929543
references: J Immunol. 1996 Dec 15;157(12):5478-86
references: 8955197
references: Genetics. 2009 Feb;181(2):593-606
references: 19015539
references: Proc Natl Acad Sci U S A. 1971 Feb;68(2):430-4
references: 4100380
references: J Exp Med. 1960 Jul 1;112:107-24
references: 13731716
references: Immunology. 1971 Jun;20(6):931-44
references: 4104284
references: Mol Ecol. 1998 Apr;7(4):453-64
references: 9628000
references: Cell. 1991 Mar 8;64(5):995-1005
references: 1900459
references: Prog Allergy. 1967;11:141-84
references: 4860380
references: J Immunol. 1985 Dec;135(6):4222-8
references: 2999240
references: J Immunol. 2002 Jun 1;168(11):5424-33
references: 12023335
references: J Immunol. 1998 Nov 15;161(10):5438-44
references: 9820519
references: Dev Comp Immunol. 2006;30(1-2):137-53
references: 16098588
references: Mol Immunol. 1980 Jan;17(1):111-7
references: 6153750
references: Cell. 1989 Oct 6;59(1):171-83
references: 2507167
references: Theor Popul Biol. 1983 Apr;23(2):216-40
references: 6612633
references: J Immunol. 1981 Aug;127(2):626-32
references: 6166680
references: Mol Immunol. 1983 Jul;20(7):753-61
references: 6412072
references: Annu Rev Biochem. 1971;40:969-1012
references: 4942225
references: J Immunol. 1976 Jan;116(1):117-25
references: 54383
references: J Immunol. 1967 Oct;99(4):737-43
references: 4963793
references: Immunogenetics. 2005 Dec;57(11):874-82
references: 16247606
references: Immunity. 1994 Nov;1(8):647-59
references: 7600292
references: Proc Natl Acad Sci U S A. 1965 Sep;54(3):864-9
references: 4160200
references: Nature. 1963 Jul 6;199:52-5
references: 14047942
references: Int Immunol. 1990;2(1):41-50
references: 2128464
references: EMBO J. 1992 Feb;11(2):603-9
references: 1537339
references: Immunogenetics. 2008 Sep;60(9):515-25
references: 18584169
references: J Immunol. 1993 Apr 1;150(7):2783-93
references: 8454855
references: Immunogenetics. 1991;33(4):255-9
references: 1902823
references: J Immunol. 1998 Mar 15;160(6):2725-9
references: 9510172
references: Mol Biol Evol. 1994 May;11(3):469-82
references: 8015440
references: Cell. 1985 Feb;40(2):283-91
references: 3917859
references: Biochem Biophys Res Commun. 1963 May 3;11:170-5
references: 13985246
references: Proc Natl Acad Sci U S A. 1987 May;84(9):3075-9
references: 3106983
references: Immunogenetics. 1999 Jul;49(7-8):629-43
references: 10369921
references: Ann Immunol (Paris). 1979 Mar-Apr;130(2):105-14
references: 111599
references: Ann Immunol (Paris). 1977 Jan-Mar;128(1-2):323-7
references: 66900
references: J Immunol. 2000 Aug 15;165(4):2012-9
references: 10925284
references: J Immunol. 1969 Jul;103(1):120-8
references: 4389618
references: J Mol Evol. 1999 Mar;48(3):369-79
references: 10093227
references: Cell. 1995 Jan 13;80(1):115-25
references: 7813007
references: Adv Immunol. 1994;56:179-218
references: 8073947
references: Proc Natl Acad Sci U S A. 1986 Jul;83(13):4883-6
references: 3014517
references: C R Hebd Seances Acad Sci. 1956 May 23;242(21):2606-8
references: 13343562
references: J Immunol. 1973 Sep;111(3):750-60
references: 4200366
references: J Immunol. 1988 Mar 1;140(5):1651-9
references: 3126232
references: Annu Rev Immunol. 1992;10:593-616
references: 1590997
references: Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6961-5
references: 7624353
references: Cell. 1990 Nov 30;63(5):987-97
references: 2124176
references: Syst Biol. 2004 Jun;53(3):433-47
references: 15503672
references: Genetics. 1991 Apr;127(4):789-99
references: 1903121
references: Eur J Immunol. 1977 Jan;7(1):15-22
references: 66147
references: J Immunol. 1998 Feb 1;160(3):1246-55
references: 9570541
references: Immunogenetics. 2008 Jan;60(1):47-55
references: 18196235
references: Cold Spring Harb Symp Quant Biol. 1974;38:507-13
references: 4524771
references: Proc Soc Exp Biol Med. 1969 Jan;130(1):48-50
references: 4179405
references: Anim Genet. 2002 Aug;33(4):309-11
references: 12139512
references: Immunochemistry. 1976 Mar;13(3):221-7
references: 819355
references: Immunochemistry. 1976 May;13(5):401-6
references: 939582
references: Cold Spring Harb Symp Quant Biol. 1977;41 Pt 2:677-86
references: 268252
references: Cell. 1990 Mar 23;60(6):963-70
references: 2317867
references: Int Arch Allergy Appl Immunol. 1968;33(1):65-88
references: 4171257
references: Mol Biol Evol. 1998 Jun;15(6):617-25
references: 9615443
references: J Immunol. 1999 Sep 15;163(6):3313-20
references: 10477601
references: J Immunol. 2004 Jan 15;172(2):1044-53
references: 14707078
references: Eur J Immunol. 1972 Dec;2(6):509-14
references: 4120276
references: Immunology. 1959 Jan;2(1):84-92
references: 13640683
references: Annu Rev Genet. 1975;9:305-53
references: 813561
references: Mol Biol Evol. 2001 Dec;18(12):2169-78
references: 11719566
references: Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9710-5
references: 10449759
references: J Immunol. 1991 Dec 1;147(11):4014-8
references: 1940383