Genomes and Genes
immunoglobulin constant regions
Summary: The domains of the immunoglobulin molecules that are invariable in their amino acid sequence within any class or subclass of immunoglobulin. They confer biological as well as structural functions to immunoglobulins. One each on both the light chains and the heavy chains comprises the C-terminus half of the IMMUNOGLOBULIN FAB FRAGMENT and two or three of them make up the rest of the heavy chains (all of the IMMUNOGLOBULIN FC FRAGMENT)
- Torres M, Fernandez Fuentes N, Fiser A, Casadevall A. The immunoglobulin heavy chain constant region affects kinetic and thermodynamic parameters of antibody variable region interactions with antigen. J Biol Chem. 2007;282:13917-27 pubmed..Furthermore, isotype affected the polyreactivity of V region identical antibodies, implying a role for C region in determining self-reactivity. ..
- Bernard O, Hozumi N, Tonegawa S. Sequences of mouse immunoglobulin light chain genes before and after somatic changes. Cell. 1978;15:1133-44 pubmed..No sequence homology was observed at or near the sites of the recombination. ..
- Hwang W, Foote J. Immunogenicity of engineered antibodies. Methods. 2005;36:3-10 pubmed..Replacement of mouse immunoglobulin constant regions with human ones effects the largest immunogenicity reduction...
- Shimizu A, Takahashi N, Yaoita Y, Honjo T. Organization of the constant-region gene family of the mouse immunoglobulin heavy chain. Cell. 1982;28:499-506 pubmed..Restriction enzyme cleavage maps of the whole constant-region gene loci were constructed with respect to eight restriction endonucleases. ..
- Saha N, Suetake H, Kikuchi K, Suzuki Y. Fugu immunoglobulin D: a highly unusual gene with unprecedented duplications in its constant region. Immunogenetics. 2004;56:438-47 pubmed publisher..The expression pattern is similar to that of IgM, corroborating the hypothesis that IgD plays an important role in the humoral immune system of this species...
- Dunnick W, Shi J, Graves K, Collins J. Germline transcription and switch recombination of a transgene containing the entire H chain constant region locus: effect of a mutation in a STAT6 binding site in the gamma 1 promoter. J Immunol. 2004;173:5531-9 pubmed..We infer that the physiologic level of germline transcription of the gamma1 gene is in excess over the amount required for efficient S recombination. ..
- Snapper C, Zelazowski P, Rosas F, Kehry M, Tian M, Baltimore D, et al. B cells from p50/NF-kappa B knockout mice have selective defects in proliferation, differentiation, germ-line CH transcription, and Ig class switching. J Immunol. 1996;156:183-91 pubmed
- Flobakk M, Rasmussen I, Lunde E, Frigstad T, Berntzen G, Michaelsen T, et al. Processing of an antigenic sequence from IgG constant domains for presentation by MHC class II. J Immunol. 2008;181:7062-72 pubmed..Comparing loop 4C(H)2 with loop 6C(H)1 mutants after injection of Ab in BALB/c mice, the former was by far the most efficient and induced specific T cell activation at concentrations at least 100-fold lower than loop 6C(H)1. ..
- Zelazowski P, Carrasco D, Rosas F, Moorman M, Bravo R, Snapper C. B cells genetically deficient in the c-Rel transactivation domain have selective defects in germline CH transcription and Ig class switching. J Immunol. 1997;159:3133-9 pubmed..Furthermore, distinct differences are revealed in the Ig isotype induction profiles of B cells lacking c-Rel activity vs those deficient in p50/nuclear factor-kappa B. ..
- Zhao Y, Pan Hammarstrom Q, Kacskovics I, Hammarstrom L. The porcine Ig delta gene: unique chimeric splicing of the first constant region domain in its heavy chain transcripts. J Immunol. 2003;171:1312-8 pubmed..However, the exon could be spliced into most of the expressed transcripts in vitro in cell transfection experiments after introduction of a single T nucleotide to restore the branchpoint sequence upstream of the putative H2 exon. ..
- Haire R, Rast J, Litman R, Litman G. Characterization of three isotypes of immunoglobulin light chains and T-cell antigen receptor alpha in zebrafish. Immunogenetics. 2000;51:915-23 pubmed..The gene sequences reported provide an essential set of markers of both B- and T-cell lineages that will facilitate investigations of immune system development. ..
- Hsu E, Pulham N, Rumfelt L, Flajnik M. The plasticity of immunoglobulin gene systems in evolution. Immunol Rev. 2006;210:8-26 pubmed
- Savan R, Aman A, Sato K, Yamaguchi R, Sakai M. Discovery of a new class of immunoglobulin heavy chain from fugu. Eur J Immunol. 2005;35:3320-31 pubmed publisher..The expression pattern of the gene has been confirmed by in situ hybridization and PCR studies...
- Bradl H, Wittmann J, Milius D, Vettermann C, Jack H. Interaction of murine precursor B cell receptor with stroma cells is controlled by the unique tail of lambda 5 and stroma cell-associated heparan sulfate. J Immunol. 2003;171:2338-48 pubmed
- Ihle Ø, Beckstrøm K, Michaelsen T. Cloning, sequencing and expression of immunoglobulin variable regions of murine monoclonal antibodies specific for the P1.7 and P1.16 PorA protein loops of Neisseria meningitidis. Scand J Immunol. 2003;57:453-62 pubmed..7- and P1.16-specific antibodies share high degree of similarities amongst each other. These V genes were used to construct chimeric antibodies with conserved antigen-binding activity. ..
- Buffo A, Zagrebelsky M, Huber A, Skerra A, Schwab M, Strata P, et al. Application of neutralizing antibodies against NI-35/250 myelin-associated neurite growth inhibitory proteins to the adult rat cerebellum induces sprouting of uninjured purkinje cell axons. J Neurosci. 2000;20:2275-86 pubmed..Together with previous observations, this suggests that these molecules regulate axonal plasticity to maintain the proper targeting of terminal arbors within specific gray matter regions. ..
- Kracker S, Bergmann Y, Demuth I, Frappart P, Hildebrand G, Christine R, et al. Nibrin functions in Ig class-switch recombination. Proc Natl Acad Sci U S A. 2005;102:1584-9 pubmed
- Pflugh D, Maher S, Bothwell A. Ly-6 superfamily members Ly-6A/E, Ly-6C, and Ly-6I recognize two potential ligands expressed by B lymphocytes. J Immunol. 2002;169:5130-6 pubmed
- Li L, Salido E, Zhou Y, Bhattacharyya S, Yannone S, Dunn E, et al. Targeted disruption of the Artemis murine counterpart results in SCID and defective V(D)J recombination that is partially corrected with bone marrow transplantation. J Immunol. 2005;174:2420-8 pubmed
- Weber E, Helps C, Foster A, Perry A, Gruffydd Jones T, Hall L, et al. Molecular cloning and phylogenetic analysis of a cDNA encoding the cat (Felis domesticus) Ig epsilon constant region. Vet Immunol Immunopathol. 2000;76:299-308 pubmed..Phylogenetic analysis of the constant regions of nine immunoglobulin epsilon genes revealed that the feline cDNA is most similar to the canine homologue. ..
- Chen Z, Earl P, Americo J, Damon I, Smith S, Yu F, et al. Characterization of chimpanzee/human monoclonal antibodies to vaccinia virus A33 glycoprotein and its variola virus homolog in vitro and in a vaccinia virus mouse protection model. J Virol. 2007;81:8989-95 pubmed
- Marchalonis J, Schluter S, Bernstein R, Hohman V. Antibodies of sharks: revolution and evolution. Immunol Rev. 1998;166:103-22 pubmed..Although the homologies between shark and mammalian immunoglobulins are unequivocal, major differences in segmental gene organization present challenges to our understanding of basic immunological phenomena such as clonal restriction. ..
- Rueff Juy D, Faure M, Drapier A, Cazenave P. Role of maternal Ig in the induction of C kappa-specific CD8+ T cell tolerance. J Immunol. 1998;161:721-8 pubmed..In addition, they strengthen the view that tolerance of CD8+ T cells to a soluble Ag is never permanently acquired even if it is present in large quantities during ontogeny. ..
- Zou Y, Gu H, Rajewsky K. Generation of a mouse strain that produces immunoglobulin kappa chains with human constant regions. Science. 1993;262:1271-4 pubmed..This technology provides a feasible option for the generation of high-affinity humanized antibodies by means of the powerful somatic hypermutation-selection mechanism. ..
- Yamawaki Kataoka Y, Kataoka T, Takahashi N, Obata M, Honjo T. Complete nucleotide sequence of immunoglobulin gamma2b chain gene cloned from newborn nouse DNA. Nature. 1980;283:786-9 pubmed
- Kelley D, Wiedemann L, Pittet A, Strauss S, Nelson K, Davis J, et al. Nonproductive kappa immunoglobulin genes: recombinational abnormalities and other lesions affecting transcription, RNA processing, turnover, and translation. Mol Cell Biol. 1985;5:1660-75 pubmed..One of the structural abnormalities discovered in this study, a large deletion which removes the entire J kappa region, also provides new insight into the mechanism of VJ and VDJ recombination. ..
- Haggart R, Perera J, Huang H. Cloning of a hamster anti-mouse CD79B antibody sequences and identification of a new hamster immunoglobulin lambda constant IGLC gene region. Immunogenetics. 2013;65:473-8 pubmed publisher..Here, we report a new hamster (Cricetulus migratorius) IG lambda constant (IGLC) gene region that is most homologous to mouse IGLC2 and IGLC3. ..
- Early P, Davis M, Kaback D, Davidson N, Hood L. Immunoglobulin heavy chain gene organization in mice: analysis of a myeloma genomic clone containing variable and alpha constant regions. Proc Natl Acad Sci U S A. 1979;76:857-61 pubmed..Southern blot analysis of embryo and myeloma DNA suggests that DNA rearrangement of heavy chain variable and constant regions occurs during the differentiation of antibody-producing cells. ..
- Haddad D, Dougier H, Laviolette N, Puget N, Khamlichi A. Replacement of Imu-Cmu intron by NeoR gene alters Imu germ-line expression but has no effect on V(D)J recombination. Mol Immunol. 2010;47:961-71 pubmed publisher..More importantly, they reveal a complex and developmentally regulated interplay between IgH enhancers in the control of Imu expression. ..
- Xiang Y, Park S, Garrard W. V? gene repertoire and locus contraction are specified by critical DNase I hypersensitive sites within the V?-J? intervening region. J Immunol. 2013;190:1819-26 pubmed publisher..Thus, our studies demonstrate that DNase I hypersensitive sites HS1-2 within the V?-J? intervening region are essential for controlling locus contraction and creating a diverse Ab repertoire. ..
- Zhao Y, Kacskovics I, Rabbani H, Hammarstrom L. Physical mapping of the bovine immunoglobulin heavy chain constant region gene locus. J Biol Chem. 2003;278:35024-32 pubmed..A further sequence comparison revealed that the bovine IGHC genes display an extensive polymorphism leading to expression of multiple antibody allotypes. ..
- Leahy D, Hendrickson W, Aukhil I, Erickson H. Structure of a fibronectin type III domain from tenascin phased by MAD analysis of the selenomethionyl protein. Science. 1992;258:987-91 pubmed..Although distinct, this topology is similar to that of immunoglobulin constant domains. An Arg-Gly-Asp (RGD) sequence that can function for cell adhesion is found in a tight turn on an exposed loop. ..
- Holash J, Davis S, Papadopoulos N, Croll S, Ho L, Russell M, et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A. 2002;99:11393-8 pubmed..VEGF-Trap-mediated blockade may be superior to that achieved by other agents, such as monoclonal antibodies targeted against the VEGF receptor. ..
- Montano R, Morrison S. Influence of the isotype of the light chain on the properties of IgG. J Immunol. 2002;168:224-31 pubmed..These studies demonstrate that the isotype of the L chain has only a slight impact on the structural and functional properties of variable region identical Abs. ..
- Zezza D, Mikoryak C, Schwager J, Steiner L. Sequence of C region of L chains from Xenopus laevis Ig. J Immunol. 1991;146:4041-7 pubmed..The similarity of the Xenopus and Rana C regions to each other is approximately the same as that of either amphibian sequence to mammalian CL. The data are discussed in terms of the evolution of kappa and lambda C regions. ..
- Bentaboulet M, Mihaesco E, Gendron M, Brouet J, Tsapis A. Genomic alterations in a case of alpha heavy chain disease leading to the generation of composite exons from the JH region. Eur J Immunol. 1989;19:2093-8 pubmed..The genomic nucleotide sequence also revealed a large deletion in the switch CH1 region which eliminated normal splicing sites and resulted in splicing of the third exon directly to the CH2 exon. ..
- Kuzin I, Ugine G, Wu D, Young F, Chen J, Bottaro A. Normal isotype switching in B cells lacking the I mu exon splice donor site: evidence for multiple I mu-like germline transcripts. J Immunol. 2000;164:1451-7 pubmed..We propose that all of these transcripts directly contribute to mu class switching activity. ..
- Ukaji T, Sumiyama D, Kai O. Partial sequence of Mongolian gerbil (Meriones unguiculatus) immunoglobulin gamma heavy chain constant region. Anim Sci J. 2011;82:713-6 pubmed publisher..6% to rat IgG1, 83.3% to rat IgG2a, 78.1% to mouse IgG1, 81.8% to mouse IgG2a, 79.1% to mouse IgG2b and 79.2% to mouse IgG3 at the nucleotide level. The results suggest that gerbil IgG is closely related to hamster IgG and rat IgG2a. ..
- McCloskey N, Turner M, Steffner P, Owens R, Goldblatt D. Human constant regions influence the antibody binding characteristics of mouse-human chimeric IgG subclasses. Immunology. 1996;88:169-73 pubmed..The exact mechanism for this phenomenon remains obscure but such differences should be taken into account when designing or choosing antibodies for therapeutic use. ..
- Menzel C, Schirrmann T, Konthur Z, Jostock T, Dubel S. Human antibody RNase fusion protein targeting CD30+ lymphomas. Blood. 2008;111:3830-7 pubmed publisher..Its modular design is set to target other internalizing tumor antigens using different antibody domains. ..
- Marcu K, Banerji J, Penncavage N, Lang R, Arnheim N. 5' flanking region of immunoglobulin heavy chain constant region genes displays length heterogeneity in germlines of inbred mouse strains. Cell. 1980;22:187-96 pubmed
- Zhou P, Ma X, Iyer L, Chaulagain C, Comenzo R. One siRNA pool targeting the ? constant region stops ? light-chain production and causes terminal endoplasmic reticulum stress. Blood. 2014;123:3440-51 pubmed publisher..This pool of siRNA can be used to reduce pathological ?-light-chain production and cause apoptosis in human plasma cells making intact IgG? antibodies. ..
- Cerutti N, Dugoujon J, Guitard E, Rabino Massa E. Gm and Km immunoglobulin allotypes in Sicily. Immunogenetics. 2004;55:674-81 pubmed..The introduction of African markers could be due to the Phoenician colonization at the end of the 2nd millennium b.c. or to the more recent Arab conquest (8th-9th centuries a.d.). ..
- Fujiki T, Tsuji A, Matsumoto S, Yamashita M, Teruya K, Shirahata S, et al. Generation of a human anti-tumor necrosis factor-? monoclonal antibody by in vitro immunization with a multiple antigen peptide. Biosci Biotechnol Biochem. 2010;74:1836-40 pubmed..This might be a good strategy for generating antigen-specific human monoclonal antibodies using a peptide antigen. ..
- Miller R, Belov K. Immunoglobulin genetics of marsupials. Dev Comp Immunol. 2000;24:485-90 pubmed..Here we review what was known prior to the cloning of marsupial Ig genes and what we have learned recently. ..
- Parseghian M, Newcomb R, Hamkalo B. Distribution of somatic H1 subtypes is non-random on active vs. inactive chromatin II: distribution in human adult fibroblasts. J Cell Biochem. 2001;83:643-59 pubmed..In a broader context, these results could explain why there are reductions in transcription in cells from mature tissue that approach senescence. ..
- Word C, White M, Kuziel W, Shen A, Blattner F, Tucker P. The human immunoglobulin C mu-C delta locus: complete nucleotide sequence and structural analysis. Int Immunol. 1989;1:296-309 pubmed..Several polymorphisms in the human population have been identified in the intergenic region and in C delta but not in C mu. ..
- Henry J, Miller M, Pontarotti P. Structure and evolution of the extended B7 family. Immunol Today. 1999;20:285-8 pubmed..They propose that B7 and MHC genes are derived from a common ancestor, with several members of this large gene family possibly having pivotal influences on T-cell activation. ..
- Shin I, Choi E, Chung J, Hwang C, Lee C, Youn H. Cloning, expression and bioassay of canine CTLA4Ig. Vet Immunol Immunopathol. 2007;118:12-8 pubmed..The findings suggest that recombinant canine CTLA4Ig protein could be valuable in assessing the function of CTLA-4 in the canine immune system and may be effective in autoimmune disease therapy. ..
- Xia Y, Pawar R, Nakouzi A, Herlitz L, Broder A, Liu K, et al. The constant region contributes to the antigenic specificity and renal pathogenicity of murine anti-DNA antibodies. J Autoimmun. 2012;39:398-411 pubmed publisher..Finally, class switch recombination may be another mechanism by which B cell autoreactivity is generated. ..
- Rush J, Liu M, Odegard V, Unniraman S, Schatz D. Expression of activation-induced cytidine deaminase is regulated by cell division, providing a mechanistic basis for division-linked class switch recombination. Proc Natl Acad Sci U S A. 2005;102:13242-7 pubmed..In addition, constitutive AID expression from a transgene accelerated division-linked CSR. Thus, we propose that the division-linked increase in AID expression provides an underlying molecular explanation for division-linked CSR. ..
- Adachi M, Kurihara Y, Nojima H, Takeda Shitaka M, Kamiya K, Umeyama H. Interaction between the antigen and antibody is controlled by the constant domains: normal mode dynamics of the HEL-HyHEL-10 complex. Protein Sci. 2003;12:2125-31 pubmed..UL2-CL could play an important role and could be attractive for modification in protein engineering. ..