Abstract
Six putative subclasses of expressed porcine IgG have been described from gene sequences and allotypic variants for five of these have been proposed. We tested this hypothesis by studying the transcription of these 11 variants in outbred hemizygous farm pigs. Since Cγ subclass genes are closely linked, they are most likely inherited as a haplotype. Since hemizygous pigs can only express genes encoded on one chromosome, identifying the expressed genes can indicate which allelic variants are linked as well as testing whether the putative alleles are indeed alleles or separate subclass genes. The procedure for producing B cell knockout pigs has recently been described; our study examines transcripts from the hemizygous parents and offspring generated by this technology. More than 570 Cγ gene clones from hemizygous animals were identified according to subclass and allotype by a combination of clone hybridization and sequencing. IgG3 accounted for 80% in newborn animals but <5% in adults. IgG1 accounted for ~50% of all clones recovered from adults and IgG4 was the least frequently recovered (4%). Results indicate that IgG1b, IgG2a, IgG3, IgG4a, IgG5a, and IgG6a are linked and also linked to IgAa. This comprises a haplotype for domesticated swine. For simplicity, we propose that the current nomenclature for the allotypes of IgG1 be reversed so that all genes in the Cγa–Cαa haplotype are designated “a”.
References
Blakeslee D, Butler JE, Stone WH (1971) Serum antigens of cattle. II. Immunogenetics of two immunoglobulin allotypes. J Immunol 107:227–235
Brown WR, Kacskovics I, Amendt B, Shinde R, Blackmore N, Rothschild M, Butler JE (1995) The hinge deletion variant of porcine IgA results from a mutation at the splice acceptor site in the first Cα intron. J Immunol 154:3836–3842
Butler JE (1974) Immunoglobulins of the mammary secretions. In: Larson BL, Smith V (eds) Lactation, a comprehensive treatise. Vol. III, chapter V. Academic, New York, pp 217–255
Butler JE (2006) Preface: why I agreed to do this. In: Antibody Repertoire Development. (J.E. Butler, Guest Ed). Developmental and Comparative Immunology 30:1–17
Butler JE, Wertz N (2006) Antibody repertoire development in fetal and neonatal piglets. XVII. IgG subclass transcription revisited with emphasis on new IgG3. J Immunol 177:5480–5489
Butler JE, Wertz N, Deschacht N, Kacskovics I (2009) Porcine IgG: structure, genetics and evolution. Immunogenetics 61:209–230
Day E (1990) Advanced immunochemistry, Sec Edth edn. Wiley, New York, pp 53–106
Dekegel M, Naessens J, Van der Loo W, Kulics J, Hamers-Casterman C, Hamers R (1981) The quarternay Gs3 and Gs7 allotypes of the rabbit: their association with the b4.1 and b4.2 alleles of the K light chain. Mol Immunol 18:561–657
Dray S, Young GO, Gerald L (1963) Immunochemical idenrtification and genetics of rabbit g-globulin allotypes. J Immunol 91:403–415
Eguchi-Ogawa T, Sun X-Z, Wertz N, Uenishi H, Puimi F, Chardon P, Wells K, Tobin GJ, Butler JE (2010) Antibody repertoire development in fetal and neonatal piglets. XI. The relationship of VDJ usage and the genomic organization of the variable heavy chain locus. J Immunol 184:3734–3742
Ein D, Fahey JL (1967) Two types of polypeptide chains in human immunoglobulins. Science 156:947–948
Janeway CA, Travere P, Walport M, Shlomchik MJ (2005) Immunobiology, 6th edn. Garland Science, New York
Kacskovics I, Sun J, Butler JE (1994) Five subclasses of swine IgG identified from the cDNA sequences of a single animal. J Immunol 153:3566–3573
Kacskovics I, Cervenak J, Erdel A, Goldsby RA, Butler JE (2011) Recent advances using FcRn overexpression in transgenic animals to overcome impediments of standard antibody technology to improve the generation of specific antibodies. mAbs 3:431–439
Kindt TJ, Todd CW (1969) Heavy and light chain allotypic markers on rabbit homocytotropic antibody. J Exp Med 130:859–866
Lefranc M-P, Lefranc G (2001) The immunoglobulin facts book. Academic, San Diego, pp 17–58
Lieberman R, Potter M (1969) Crossing-over between genes in the immunoglobulin heavy chain linkage group of the mouse. J Exp Med 130:519–541
Mendicino M, Ramsoondar J, Phelps C, Vaught T, Ball S, ReRoith T, Monahan J, Chen S, Dandro A, Boone J, Jobst P, Vance A, Wertz N, Bergman Z, Sun X-Z, Polejaeva I, Butler JE, Dai Y, Ayares D, Wells K (2011) Targeted disruption of the porcine immunoglobulin heavy chain locus produces a null phenotype. Transgenic Res 20:625–641
Mossman TR, Coffman RL (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7:143–173
Navarro P, Christenson R, Ekhardt G, Lunney JK, Rothschild M, Bosworth B, Lemke J, Butler JE (2000) Genetic differences in the frequency of the hinge variants of porcine IgA is breed dependent. Vet Immunol Immunopath 73:287–295
Rathbun G, Berman J, Yancopoulos G, Alt FW Jr (1989) Organization and expression of the mammalian heavy-chain variable-region locus. In: Honjo T, Alt FW, Rabbitts TH (eds) Immunoglobulin genes. Academic, London, pp 63–90
Roitt I, Brostoff J, Male D (2011) Immunology. Mosby, New York, 480pp
Roopenian DC, Akilesh S (2007) FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 7:715–725
Ropartz C, Lenoir J, Rivat L (1961) A new inheritable property of human sera. The InV factor. Nature 189:586
Shimizu A, Takahashi N, Yaoita Y, Honjo T (1982) Organization of the constant-region gene gamily of the mouse immunoglobulin heavy chain. Cell 28:499–506
Sun J, Butler JE (1996) Molecular characteristics of VDJ transcripts from a newborn piglet. Immunology 88:331–339
Ward SE, Ober RJ (2009) Multitasking by exploitation of intracelluar transport functions: the many faces of FcRn. Adv Immunol 103:77–115
Acknowledgment
The work described constitutes partial fulfillment for a BA degree in Microbiology at the University of Iowa. This research is supported by: NSF-IOS grant 0077237, grant 07–210 from the National Porkboard, and USDA-AFRI NIFA/DHS grant 2010-39559-21860.
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Kloep, A., Wertz, N., Mendicino, M. et al. Linkage haplotype for allotypic variants of porcine IgA and IgG subclass genes. Immunogenetics 64, 469–473 (2012). https://doi.org/10.1007/s00251-012-0603-7
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DOI: https://doi.org/10.1007/s00251-012-0603-7