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Gene Review

Ighg2b  -  immunoglobulin heavy constant gamma 2B

Mus musculus

Synonyms: Ig gamma-2B chain C region, IgG2b, Igh-3, gamma2b
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Disease relevance of Igh-3

  • Extensive mapping of the recombinant phages and Southern blot analysis with several restriction enzymes gave the complete organization of these loci: gamma 2b (18 kb) gamma 2c (17 kb) gamma 2a (14 kb) epsilon [1].
  • 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 [2].
  • In the nude mice experiment, only the IgG2a variant inhibited growth of human colorectal carcinoma, while IgG1 and IgG2b were ineffective [3].
  • Northern blots indicated that the transfected gamma 2b gene was processed in a manner similar to the endogenous heavy chain in both lymphoma and myeloma cells [4].
  • A series of mouse myeloma mutants, derived from a cell line of the murine MPC-11 tumor (gamma 2b, kappa), resemble human heavy-chain disease in their loss of an internal domain (exon) [5].

Psychiatry related information on Igh-3

  • We report the isolation and characterization of a mouse autoanti-idiotypic mAb (D7.4 IgG2a), which is directed against a major public Id (A52 IgG2b) in the murine and human autoimmune response to DNA [6].

High impact information on Igh-3

  • Two gamma 2b-producing cell lines that did not have other cytoplasmic heavy chains or light chains were established from A-MuLV-transformed cell lines [7].
  • It appears that among the 134 differences between the two gamma 2a alleles, 70 are at positions where gamma 2a and gamma 2b are identical in the BALB/c haplotype and 54 are at positions where gamma 2a and gamma 2b are identical in the C57BL/6 haplotype [8].
  • Gene conversion and polymorphism: generation of mouse immunoglobulin gamma 2a chain alleles by differential gene conversion by gamma 2b chain gene [8].
  • The nucleotide sequences of the S gamma 1, S gamma 2b and S gamma 3 repeating units share significant homology with each other [9].
  • We have cloned a rearranged gamma 2b gene from a mouse myeloma (MPC11) and compared its structure with the germ line counterparts [9].

Chemical compound and disease context of Igh-3


Biological context of Igh-3

  • The rearranged gamma 2b gene contained the 5' flanking region of the gamma 3 gene (S gamma 3 region) which are linked to the 5' flanking region of the gamma 2b gene (S gamma 2b region) [9].
  • The first exon of this M gene segment has been identified in chromosomal gamma 1 and gamma 2b gene clones by its sequence homology with the corresponding exon in the mu gene [15].
  • The second type of recombination replaces the exons coding for the constant region of the mu chain with those coding for the same region of the gamma 2b chain [16].
  • This report demonstrates that transforming growth factor (TGF) beta 1, previously shown to induce IgA class switching, selectively stimulates IgG2b secretion by BALB/c resting B cells activated with LPS [17].
  • These results indicate that structural genes for the gamma 2b-, mu-, and alpha-heavy chain-constant regions map to the distal half of this chromosome [18].

Anatomical context of Igh-3

  • The presence of T cells resulted in a preferential enhancement of the production of anti-TNP Ab of those IgG subclasses which were least represented in the absence of T cells, i.e., IgG2b and IgG2a [19].
  • 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 [20].
  • To determine the chromosomal location of mouse immunoglobulin heavy chain structural genes unambiguously, a panel of somatic cell hybrids was scored for the presence of DNA sequences homologous to gamma 2b-, mu-, and alpha-heavy chain-constant region DNA probe molecules [18].
  • Three different monoclonal antibody isotypes, IgG1, IgG2b, and IgG2a, were derived by selection of isotype-switch variants from the CO-19-9 hybridoma [3].
  • 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 [3].

Associations of Igh-3 with chemical compounds

  • Bacterial lipopolysaccharide (LPS) has been reported to induce immunoglobulin (Ig)G2b class switching, yet we observed strain differences in IgG2b secretion in response to this mitogen [17].
  • In the absence of T cells, B cells were found to respond to the type 2 T-independent (TI-2) antigen, trinitrophenyl (TNP)-Ficoll, with a characteristic hierarchy of IgM and IgG subclass Ab production which directly correlated with 5' to 3' Igh-C gene order, i.e., IgM greater tha IgG3 greater than IgG1 greater than IgG2b greater than IgG2a [21].
  • Analysis of the carbohydrate moieties of the gamma 1 chain from the homodimeric and heterodimeric IgGs and of the gamma 2b chain from the heterodimeric molecule demonstrates that the polypeptide structure of the heavy chain influences the terminal galactosylation of the glycan unit at the conserved site of glycosylation of IgGs [22].
  • Two fragments from IgG2a--one one from the CH2 domain, differing by only four amino acids from the homologous IgG2b fragment, and the other from the CH3 domain--specifically bound to the gamma 2a Fc receptor [23].
  • Site of binding of IgG2b and IgG2a by mouse macrophage Fc receptors by using cyanogen bromide fragments [23].

Physical interactions of Igh-3

  • IgG2b CD20 mAbs interacted preferentially with intermediate affinity FcgammaRIV [24].
  • Rather, binding of the fragment from the CH3 domain of IgG2a augmented the binding of the fragment from the CH2 domain of IgG2a but not that of the homologous fragment from IgG2b [23].
  • In addition, we mutated the Glu 333, which resides in close proximity to the postulated C1q-binding site of mouse IgG2b, as well as Leu 235 in the lower hinge region [25].
  • Pooled regressor sera contained IgM, IgG2a, and IgG2b antibodies which bound to M-MuLV-expressing lymphoma cells [26].
  • These data indicate that Fc receptor binding of IgG2b results from the concerted action of membrane lipid and protein [27].

Regulatory relationships of Igh-3

  • The arthritis induced with the IgG1 and IgG2b Ab was also inhibited by FcgammaRIII disruption, whereas arthritis mediated by the IgG2a Ab was not substantially affected [28].
  • Finally, TGF-beta 1 failed to stimulate IgG2b secretion by B cells activated with dextran-conjugated anti-IgD antibody [17].
  • The C(H)1 and transmembrane domains of mu in the context of a gamma2b transgene do not suffice to promote B cell maturation [29].
  • IgG1 and IgG2b levels did not increase in B. burgdorferi infected mice treated with anti-IL-12 mAb compared with controls suggesting that Th2 responses were not affected [30].
  • 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 [31].

Other interactions of Igh-3


Analytical, diagnostic and therapeutic context of Igh-3


  1. Further evidence that BALB/c and C57BL/6 gamma 2a genes originate from two distinct isotypes. Morgado, M.G., Cam, P., Gris-Liebe, C., Cazenave, P.A., Jouvin-Marche, E. EMBO J. (1989) [Pubmed]
  2. 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]
  3. Isolation and characterization of anti-monosialoganglioside monoclonal antibody 19-9 class-switch variants. Steplewski, Z., Spira, G., Blaszczyk, M., Lubeck, M.D., Radbruch, A., Illges, H., Herlyn, D., Rajewsky, K., Scharff, M. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  4. Sequences near the 3' secretion-specific polyadenylation site influence levels of secretion-specific and membrane-specific IgG2b mRNA in myeloma cells. Kobrin, B.J., Milcarek, C., Morrison, S.L. Mol. Cell. Biol. (1986) [Pubmed]
  5. Loss of a consensus splice signal in a mutant immunoglobulin gene eliminates the CH1 domain exon from the mRNA. Brandt, C.R., Morrison, S.L., Birshtein, B.K., Milcarek, C. Mol. Cell. Biol. (1984) [Pubmed]
  6. Structure and binding properties of a monoclonal anti-idiotypic autoantibody to anti-DNA with epibody activity. Fischel, R., Eilat, D. J. Immunol. (1992) [Pubmed]
  7. Isotype switching in murine pre-B cell lines. Akira, S., Sugiyama, H., Yoshida, N., Kikutani, H., Yamamura, Y., Kishimoto, T. Cell (1983) [Pubmed]
  8. Gene conversion and polymorphism: generation of mouse immunoglobulin gamma 2a chain alleles by differential gene conversion by gamma 2b chain gene. Ollo, R., Rougeon, F. Cell (1983) [Pubmed]
  9. Repetitive sequences in class-switch recombination regions of immunoglobulin heavy chain genes. Kataoka, T., Miyata, T., Honjo, T. Cell (1981) [Pubmed]
  10. Immunogenicity of Streptococcus pneumoniae type 14 capsular polysaccharide: influence of carriers and adjuvants on isotype distribution. van de Wijgert, J.H., Verheul, A.F., Snippe, H., Check, I.J., Hunter, R.L. Infect. Immun. (1991) [Pubmed]
  11. 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]
  12. Identification of soluble Fc receptors in mouse serum and the conditioned medium of stimulated B cells. Pure, E., Durie, C.J., Summerill, C.K., Unkeless, J.C. J. Exp. Med. (1984) [Pubmed]
  13. Protection of trinitrobenzene sulfonic acid-induced colitis by an interleukin 2-IgG2b fusion protein in mice. Stallmach, A., Wittig, B., Giese, T., Pfister, K., Hoffmann, J.C., Bulfone-Paus, S., Kunzendorf, U., Meuer, S.C., Zeitz, M. Gastroenterology (1999) [Pubmed]
  14. Antitumor effect of adriamycin entrapped in liposomes conjugated with anti-human alpha-fetoprotein monoclonal antibody. Konno, H., Suzuki, H., Tadakuma, T., Kumai, K., Yasuda, T., Kubota, T., Ohta, S., Nagaike, K., Hosokawa, S., Ishibiki, K. Cancer Res. (1987) [Pubmed]
  15. Gene segments encoding transmembrane carboxyl termini of immunoglobulin gamma chains. Rogers, J., Choi, E., Souza, L., Carter, C., Word, C., Kuehl, M., Eisenberg, D., Wall, R. Cell (1981) [Pubmed]
  16. Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy-chain genes. Sakano, H., Maki, R., Kurosawa, Y., Roeder, W., Tonegawa, S. Nature (1980) [Pubmed]
  17. Transforming growth factor beta 1 selectivity stimulates immunoglobulin G2b secretion by lipopolysaccharide-activated murine B cells. McIntyre, T.M., Klinman, D.R., Rothman, P., Lugo, M., Dasch, J.R., Mond, J.J., Snapper, C.M. J. Exp. Med. (1993) [Pubmed]
  18. Chromosomal location of the structural gene cluster encoding murine immunoglobulin heavy chains. D'Eustachio, P., Pravtcheva, D., Marcu, K., Ruddle, F.H. J. Exp. Med. (1980) [Pubmed]
  19. IgG subclass, IgE, and IgA anti-trinitrophenyl antibody production within trinitrophenyl-Ficoll-responsive B cell clones. Evidence in support of three distinct switching pathways. Mongini, P.K., Paul, W.E., Metcalf, E.S. J. Exp. Med. (1983) [Pubmed]
  20. 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]
  21. T cell regulation of immunoglobulin class expression in the antibody response to trinitrophenyl-ficoll. Evidence for T cell enhancement of the immunoglobulin class switch. Mongini, P.K., Paul, W.E., Metcalf, E.S. J. Exp. Med. (1982) [Pubmed]
  22. The polypeptide of immunoglobulin G influences its galactosylation in vivo. Lee, S.O., Connolly, J.M., Ramirez-Soto, D., Poretz, R.D. J. Biol. Chem. (1990) [Pubmed]
  23. Site of binding of IgG2b and IgG2a by mouse macrophage Fc receptors by using cyanogen bromide fragments. Diamond, B., Boccumini, L., Birshtein, B.K. J. Immunol. (1985) [Pubmed]
  24. 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]
  25. Lysine 322 in the human IgG3 C(H)2 domain is crucial for antibody dependent complement activation. Thommesen, J.E., Michaelsen, T.E., Løset GA, n.u.l.l., Sandlie, I., Brekke, O.H. Mol. Immunol. (2000) [Pubmed]
  26. Isotype distribution and specificity of the antibody response to primary Moloney murine sarcoma virus infection in BALB/c mice. Powell, T.J., Gaupp, B., Epps, J.M., Srinivas, R.V., Lamon, E.W. Viral Immunol. (1989) [Pubmed]
  27. The murine macrophage Fc receptor for IgG2b is lipid dependent. Anderson, C.L. J. Immunol. (1980) [Pubmed]
  28. Induction of arthritis by single monoclonal IgG anti-collagen type II antibodies and enhancement of arthritis in mice lacking inhibitory FcgammaRIIB. Nandakumar, K.S., Andrén, M., Martinsson, P., Bajtner, E., Hellström, S., Holmdahl, R., Kleinau, S. Eur. J. Immunol. (2003) [Pubmed]
  29. The C(H)1 and transmembrane domains of mu in the context of a gamma2b transgene do not suffice to promote B cell maturation. Shen, X., Bozek, G., Pinkert, C.A., Storb, U. Int. Immunol. (1999) [Pubmed]
  30. Effect of anti-interleukin 12 treatment on murine lyme borreliosis. Anguita, J., Persing, D.H., Rincon, M., Barthold, S.W., Fikrig, E. J. Clin. Invest. (1996) [Pubmed]
  31. 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]
  32. FcgammaRIV: a novel FcR with distinct IgG subclass specificity. Nimmerjahn, F., Bruhns, P., Horiuchi, K., Ravetch, J.V. Immunity (2005) [Pubmed]
  33. 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]
  34. Immunoglobulin VH region genes of the mouse are organized in overlapping clusters. Blankenstein, T., Krawinkel, U. Eur. J. Immunol. (1987) [Pubmed]
  35. Cloning immunoglobulin gamma 2b chain gene of mouse: characterization and partial sequence determination. Kataoka, T., Yamawaki-Kataoka, Y., Yamagishi, H., Honjo, T. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  36. DNA rearrangements affecting both variable and constant regions of Ig H chain genes in MPC11 mouse myeloma variants. Gilmore, G.L., Bard, J.A., Birshtein, B.K. J. Immunol. (1988) [Pubmed]
  37. Two distinct mechanisms of antitumor activity mediated by the combination of interleukin 2 and monoclonal antibodies. Vuist, W.M., van Buitenen, F., Hekman, A., Melief, C.J. Cancer Res. (1990) [Pubmed]
  38. Dual roles for IFN-gamma, but not for IL-4, in spontaneous autoimmune thyroiditis in NOD.H-2h4 mice. Yu, S., Sharp, G.C., Braley-Mullen, H. J. Immunol. (2002) [Pubmed]
  39. Hapten-induced model of murine inflammatory bowel disease: mucosa immune responses and protection by tolerance. Elson, C.O., Beagley, K.W., Sharmanov, A.T., Fujihashi, K., Kiyono, H., Tennyson, G.S., Cong, Y., Black, C.A., Ridwan, B.W., McGhee, J.R. J. Immunol. (1996) [Pubmed]
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