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Gene Review

Ighg1  -  immunoglobulin heavy constant gamma 1 (G1m...

Mus musculus

Synonyms: IgG1, Igh-4, VH7183
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Disease relevance of Ighg1

  • In the nude mice experiment, only the IgG2a variant inhibited growth of human colorectal carcinoma, while IgG1 and IgG2b were ineffective [1].
  • As has been shown with conventional antibodies, monoclonal IgG1 and IgE are the two classes capable of sensitizing the mouse for anaphylactic reactions, IgE sensitizes the rat, and IgG2a sensitizes the guinea pig [2].
  • Small amounts of membrane gamma mRNAs persist in plasmacytomas secreting IgG1, IgG2a, or IgG2b, suggesting that competition between alternative RNA processing pathways governs the synthesis of membrane and secretory gamma chain mRNAs [3].
  • Peritoneal mast cells, bone marrow-derived mast cells (BMMC), and the mastocytoma cells P815 were found to bear trypsin-resistant, 2.4G2+, low-affinity receptors binding mouse monoclonal IgG1, IgG2a, and IgG2b, i.e., Fc gamma RII [4].
  • SCID mice were found to have rapid blood clearance of injected mouse IgG2a antibodies (Ab), while IgG1 Ab were cleared normally [5].

High impact information on Ighg1

  • The extent of segmental flexibility in times of nanoseconds and the capacity to fix complement were greatest for IgG2b, intermediate for IgG2a, and least for IgG1 and IgE [6].
  • Here, we demonstrate that mice deficient for the ligand-binding alpha chain of Fc gamma RIII lack NK cell-mediated antibody-dependent cytotoxicity and phagocytosis of IgG1-coated particles by macrophages [7].
  • In addition, the transgenes lacking the 3' end of the locus express reduced amounts of gamma1 germline transcripts and 2-3% of the amount of Tg IgG1 in tissue culture compared with intact transgenes [8].
  • In contrast, erythrocyte-binding affinities only played a minor role in in vivo hemolytic activities of the IgG1 and IgG2a isotypes of 34-3C and 4C8 antibodies, where complement was not or only partially involved, respectively [9].
  • Passive administration of an IgG1 mAb protects FcRgamma+/- mice infected with C. neoformans, but fails to protect FcRgamma-/- mice, indicating that the gamma chain acting through FcgammaRI and/or III is essential for IgG1-mediated protection [10].

Chemical compound and disease context of Ighg1


Biological context of Ighg1


Anatomical context of Ighg1

  • Mouse macrophages have two FcRs-FcRI, which is trypsin-sensitive and binds IgG2a, and FcRII, which is trypsin-resistant and binds IgG2b and IgG1 complexes [19].
  • IgG1 CD20 mAbs induced B cell depletion through preferential, if not exclusive, interactions with low-affinity FcgammaRIII [20].
  • The 34-3C autoantibody opsonizing extensively circulating erythrocytes efficiently activated complement in vivo (IgG2a = IgG2b > IgG3), except for the IgG1 isotype, while the 4C8 IgG autoantibody failed to activate complement [9].
  • Three different monoclonal antibody isotypes, IgG1, IgG2b, and IgG2a, were derived by selection of isotype-switch variants from the CO-19-9 hybridoma [1].
  • Analysis of the binding of three isotypes to the human FcR expressed by U937 cells induced by gamma interferon has shown that only IgG2a proteins bound to high-affinity FcR, but not IgG1 or IgG2b variants [1].

Associations of Ighg1 with chemical compounds

  • The predominant serum IgG subclass response to O139 lipopolysaccharide was initially IgG3 until day 56, after which IgG1 was predominant [21].
  • When preformed complexes were added to serum, those containing IgG2 or IgM were potent activators of C4, whilst IgG1 complexes were less efficient [22].
  • C3 activation in normal serum was similar for complexes containing IgG1, IgG2a, IgG2b or IgM [22].
  • Intact antibodies (mouse monoclonal antibodies [MoAbs] IgG1 and IgG2b, human immune heat-inactivated serum [predominantly IgG1], and IgG purified from human immune serum) that block the sialic acid-binding site on HA significantly reduced (> 80%) neutrophil adherence to influenza-infected epithelial cells [23].
  • Capsule-specific IgG1 and IgG2 Abs are induced upon vaccination with polysaccharide-based vaccines that mediate host protection [24].

Physical interactions of Ighg1

  • This conclusion is supported by the observation that after proteolysis, the Fc gamma RII-mediated binding of EA-mouse IgG1 becomes susceptible to inhibition by (monomeric) human IgG [25].
  • Incubation of neutrophils with a mAb against the FcRIII completely blocked the binding of IgG1 complexes and IgG3 complexes [26].
  • The COOH terminus of the IgG2 CH2 domain was found to contain accessory site(s) since it enhanced the binding properties of both IgG1 PLLGG and native IgG1 [27].

Regulatory relationships of Ighg1

  • These adjuvants not only enhanced the amount of IgG evoked but also shifted the IgG subclass distribution from mainly IgG1 toward the complement-activating subclasses IgG2a and IgG2b [28].
  • In contrast, absence of the inhibiting FcgammaRIIB augmented the Hg-induced increase of both serum IgG1 and IgE [29].

Other interactions of Ighg1

  • We found new allotypes of the Igh-1 and Igh-4 loci [30].
  • It is reported here that rat IgG1 antibodies, which are associated in the rat with a Th1-type response, act as highly effective blocking antibodies over a wide concentration range [31].
  • Mouse immunoglobulin epsilon chain gene was cloned from DNA of a hybridoma producing anti-dinitrophenyl IgE, which was constructed by fusing a spleen cell of a BALB/c mouse with a variant clone of MOPC21 myeloma (IgG1 producer) [32].
  • For example, two independently produced IgG1 monoclonal reagents raised against the Igh-1b allotype were poorly suppressive or nonsuppressive, whereas an IgG3 and an IgG2a monoclonal antibody induced a 90% suppression of the target allotype in transferred adult SC [33].
  • Probably as a consequence of this reduction in mature B cells, Bob1-deficient mice show reduced serum titers of the immunoglobulin isotypes IgG1, IgG2a, IgG2b and IgA, but not IgM [34].

Analytical, diagnostic and therapeutic context of Ighg1

  • We also found an increase in total protein (TP) level and IL-5 production in bronchoalveolar lavage (BAL) fluid and an increase in SRW-specific Th2-type immunoglobulins (IgG1, IgG2b) and total serum IgE levels [35].
  • The segmental flexibility and complement fixation activity were measured of six genetically engineered molecules (the four human IgG isotypes, mouse IgG3 and rabbit IgG) and the remaining three mouse IgG isotypes, (IgG1, IgG2a and IgG2b), isolated previously by somatic cell genetic techniques [36].
  • In flow cytometry, there was weak reactivity with granulocytes, a reactivity also observed with two previously described highly specific Le(y) mouse mAbs--BR55-2 (IgG3) and B3 (IgG1) [37].
  • Thus, 7S IgG1, 7S IgG2, 7S IgG2a, and 7S IgG2b were obtained which were completely pure by criteria of immunodiffusion and immunoelectrophoresis [38].
  • Stable F(ab')2 can be produced in good yield from IgG1 with pepsin at pH 3.5 to 4.0 and can be made directly by pepsin treatment of ascites fluids or cell culture supernatants containing IgG1 [39].


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  2. Biological activities of antitrinitrophenyl and antidinitrophenyl mouse monoclonal antibodies. Hirayama, N., Hirano, T., Köhler, G., Kurata, A., Okumura, K., Ovary, Z. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  3. mRNA for surface immunoglobulin gamma chains encodes a highly conserved transmembrane sequence and a 28-residue intracellular domain. Tyler, B.M., Cowman, A.F., Gerondakis, S.D., Adams, J.M., Bernard, O. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
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  5. Rapid blood clearance of injected mouse IgG2a in SCID mice. Michel, R.B., Ochakovskaya, R., Mattes, M.J. Cancer Immunol. Immunother. (2002) [Pubmed]
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  7. Impaired IgG-dependent anaphylaxis and Arthus reaction in Fc gamma RIII (CD16) deficient mice. Hazenbos, W.L., Gessner, J.E., Hofhuis, F.M., Kuipers, H., Meyer, D., Heijnen, I.A., Schmidt, R.E., Sandor, M., Capel, P.J., Daëron, M., van de Winkel, J.G., Verbeek, J.S. Immunity (1996) [Pubmed]
  8. The 3' end of the heavy chain constant region locus enhances germline transcription and switch recombination of the four gamma genes. Dunnick, W.A., Shi, J., Graves, K.A., Collins, J.T. J. Exp. Med. (2005) [Pubmed]
  9. Complement activation selectively potentiates the pathogenicity of the IgG2b and IgG3 isotypes of a high affinity anti-erythrocyte autoantibody. Azeredo da Silveira, S., Kikuchi, S., Fossati-Jimack, L., Moll, T., Saito, T., Verbeek, J.S., Botto, M., Walport, M.J., Carroll, M., Izui, S. J. Exp. Med. (2002) [Pubmed]
  10. Antibody-mediated modulation of Cryptococcus neoformans infection is dependent on distinct Fc receptor functions and IgG subclasses. Yuan, R., Clynes, R., Oh, J., Ravetch, J.V., Scharff, M.D. J. Exp. Med. (1998) [Pubmed]
  11. Increased efficacy of the immunoglobulin G2a subclass in antibody-mediated protection against lactate dehydrogenase-elevating virus-induced polioencephalomyelitis revealed with switch mutants. Markine-Goriaynoff, D., Coutelier, J.P. J. Virol. (2002) [Pubmed]
  12. Production and characterization of monoclonal antibodies to the EDTA extract of Leptospira interrogans, serovar icterohaemorrhagiae. Leite, L.T., Resende, M., de Souza, W., Camargos, E.R., Koury, M.C. Rev. Soc. Bras. Med. Trop. (1996) [Pubmed]
  13. Tidal midexpiratory flow as a measure of airway hyperresponsiveness in allergic mice. Glaab, T., Daser, A., Braun, A., Neuhaus-Steinmetz, U., Fabel, H., Alarie, Y., Renz, H. Am. J. Physiol. Lung Cell Mol. Physiol. (2001) [Pubmed]
  14. Restriction fragment length polymorphism and evolution of the mouse immunoglobulin constant region gamma loci. Morgado, M.G., Jouvin-Marche, E., Gris-Liebe, C., Bonhomme, F., Anand, R., Talwar, G.P., Cazenave, P.A. Immunogenetics (1993) [Pubmed]
  15. Nucleotide sequences of gene segments encoding membrane domains of immunoglobulin gamma chains. Yamawaki-Kataoka, Y., Nakai, S., Miyata, T., Honjo, T. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  16. Functional polymorphisms of Fc receptors in human monocyte-mediated cytotoxicity towards erythrocytes induced by murine isotype switch variants. Boot, J.H., Geerts, M.E., Aarden, L.A. J. Immunol. (1989) [Pubmed]
  17. Defective Fc gamma RII gene expression in macrophages of NOD mice: genetic linkage with up-regulation of IgG1 and IgG2b in serum. Luan, J.J., Monteiro, R.C., Sautès, C., Fluteau, G., Eloy, L., Fridman, W.H., Bach, J.F., Garchon, H.J. J. Immunol. (1996) [Pubmed]
  18. Dissociation kinetics between a mouse Fc receptor (Fc gamma RII) and IgG: measurement by total internal reflection with fluorescence photobleaching recovery. Hsieh, H.V., Thompson, N.L. Biochemistry (1995) [Pubmed]
  19. Monoclonal anti-Fc receptor IgG blocks antibody enhancement of viral replication in macrophages. Peiris, J.S., Gordon, S., Unkeless, J.C., Porterfield, J.S. Nature (1981) [Pubmed]
  20. Antibody isotype-specific engagement of Fcgamma receptors regulates B lymphocyte depletion during CD20 immunotherapy. Hamaguchi, Y., Xiu, Y., Komura, K., Nimmerjahn, F., Tedder, T.F. J. Exp. Med. (2006) [Pubmed]
  21. Long-term systemic and mucosal antibody responses measured in BALB/c mice following intranasal challenge with viable enterotoxigenic Escherichia coli. Byrd, W., Cassels, F.J. FEMS Immunol. Med. Microbiol. (2006) [Pubmed]
  22. The activation of C3 and C4 in human serum by immune complexes containing mouse monoclonal antibodies of different isotype and affinity: effects on solubilisation. Stewart, W.W., Johnson, A., Steward, M.W., Whaley, K., Kerr, M.A. Mol. Immunol. (1988) [Pubmed]
  23. Neutrophils do not bind to or phagocytize human immune complexes formed with influenza virus. Ratcliffe, D.R., Michl, J., Cramer, E.B. Blood (1993) [Pubmed]
  24. Central role of complement in passive protection by human IgG1 and IgG2 anti-pneumococcal antibodies in mice. Saeland, E., Vidarsson, G., Leusen, J.H., Van Garderen, E., Nahm, M.H., Vile-Weekhout, H., Walraven, V., Stemerding, A.M., Verbeek, J.S., Rijkers, G.T., Kuis, W., Sanders, E.A., Van De Winkel, J.G. J. Immunol. (2003) [Pubmed]
  25. Proteolysis induces increased binding affinity of the monocyte type II FcR for human IgG. van de Winkel, J.G., van Ommen, R., Huizinga, T.W., de Raad, M.A., Tuijnman, W.B., Groenen, P.J., Capel, P.J., Koene, R.A., Tax, W.J. J. Immunol. (1989) [Pubmed]
  26. Binding characteristics of dimeric IgG subclass complexes to human neutrophils. Huizinga, T.W., Kerst, M., Nuyens, J.H., Vlug, A., von dem Borne, A.E., Roos, D., Tetteroo, P.A. J. Immunol. (1989) [Pubmed]
  27. Identification of a secondary Fc gamma RI binding site within a genetically engineered human IgG antibody. Chappel, M.S., Isenman, D.E., Oomen, R., Xu, Y.Y., Klein, M.H. J. Biol. Chem. (1993) [Pubmed]
  28. Meningococcal lipopolysaccharide (LPS)-derived oligosaccharide-protein conjugates evoke outer membrane protein- but not LPS-specific bactericidal antibodies in mice: influence of adjuvants. Verheul, A.F., Van Gaans, J.A., Wiertz, E.J., Snippe, H., Verhoef, J., Poolman, J.T. Infect. Immun. (1993) [Pubmed]
  29. The role of Fc-receptors in murine mercury-induced systemic autoimmunity. Martinsson, K., Hultman, P. Clin. Exp. Immunol. (2006) [Pubmed]
  30. New immunoglobulin IgG allotypes and haplotypes found in wild mice with monoclonal anti-allotope antibodies. Huang, C.M., Parsons, M., Wakeland, E.K., Moriwaki, K., Herzenberg, L.A. J. Immunol. (1982) [Pubmed]
  31. The effectiveness of different rat IgG subclasses as IgE-blocking antibodies in the rat basophil leukaemia cell model. Philips, J.R., Brouwer, W., Edwards, M., Mahler, S., Ruhno, J., Collins, A.M. Immunol. Cell Biol. (1999) [Pubmed]
  32. Cloning of mouse immunoglobulin epsilon gene and its location within the heavy chain gene cluster. Nishida, Y., Kataoka, T., Ishida, N., Nakai, S., Kishimoto, T., Böttcher, I., Honjo, T. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  33. Antibody-mediated allotype suppression in adult mice: the role of antigen, effector isotype and regulatory T cells. Curling, E.M., Dresser, D.W. Eur. J. Immunol. (1984) [Pubmed]
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  35. Short ragweed allergen induces eosinophilic lung disease in HLA-DQ transgenic mice. Chapoval, S.P., Nabozny, G.H., Marietta, E.V., Raymond, E.L., Krco, C.J., Andrews, A.G., David, C.S. J. Clin. Invest. (1999) [Pubmed]
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