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Gene Review

IgG-2a  -  gamma-2a immunoglobulin heavy chain

Rattus norvegicus

Synonyms: Ig gamma-2A chain C region, Igg-2a
 
 
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Disease relevance of IgG-2a

 

High impact information on IgG-2a

  • We have previously reported the production of a rat monoclonal IgG2a antibody against Schistosoma mansoni which exhibits marked cytoxicity for schistosomula in the presence of eosinophils and a high degree of protection by passive transfer in naive rats [6].
  • These findings coincided with a predominant humoral response to the cyanogen bromide (CB) 11 fragment of the human CII molecule by the pathogenic IgG2a isotype [7].
  • Specificity of fc receptors for IgG2a, IgG1/IgG2b, and IgE on rat macrophages [8].
  • Tolerance was tested in the BWF1 B cells by preincubating them with DNP-murine IgG2a (MGG), which can induce tolerance in BALB/c cell line lymphocytes [9].
  • Four selected monoclonal antibodies were all of the IgG 2a subclass type kappa and bound to protein A. One monoclonal antibody (23.8B6) was shown to be directed toward the C-terminal region and another (23.6B4) toward the N-terminal to central region of the glucagon molecule [10].
 

Chemical compound and disease context of IgG-2a

  • Furthermore, lower total immunoglobulin G (IgG) levels (P < 0.01) and higher IgG2a levels (P < 0.025) in serum against P. aeruginosa sonicate and a shift from an acute type to a chronic type of lung inflammation compared to those in the control and cortisone-treated groups were observed [11].
 

Biological context of IgG-2a

  • To further characterize this immunodeficiency in antibody production, we have quantified the immunoglobulin G (IgG) subclasses (IgG1, IgG2a, IgG2b, and IgG2c) during the primary and secondary response to TT in normal, vitamin A-deficient, and retinol-repleted rats [12].
  • Effect of intraperitoneal injection volume and antibody protein dose on the pharmacokinetics of intraperitoneally administered IgG2a kappa murine monoclonal antibody in the rat [13].
  • IgE injected i.p. 24 hr before the sensitization with IgE anti-ovalbumin (OVA) completely inhibited both IgE- and IgG2a-induced passive cutaneous anaphylactic (PCA) reactions at a dose (2.5 mg/100 g body weight) that resulted in peak serum concentrations of 150 micrograms IgE IR162/ml [14].
  • Similarly, the kinetics and intensity of effector responses such as OVA-specific IgG2a and IgE synthesis were neither increased nor decreased in any of the three models examined [15].
  • Given that IFN-gamma is an important regulator of the IgM to IgG2a switch, it is possible that the small rise in GC found 4-7 days after KLH facilitates IgG2a isotype switching [16].
 

Anatomical context of IgG-2a

  • Four of the monoclonal hybridoma cell lines secreted IgM antibodies; two, IgG1; three, IgG2a; and one, IgG2b [17].
  • The results of in vitro experiments showed that peritoneal exudate cells were able to inhibit the proliferation of Daudi cells in the presence of the IgG2a isotype variant of CLB-CD19 mAb but not in the presence of the other CLB-CD19 mAb isotype variants [18].
  • Rosette formation using S. mansoni antigen-coated erythrocytes was used to demonstrate the presence of anti-S. mansoni IgG2a antibody at the surface of infected eosinophils [19].
  • These changes in IgE and IgG2a responsiveness are Ag specific and T cell dependent [20].
  • The Fc portion of IgG2a immunoglobulins therefore seemed to be involved in binding to the mast cell surface [21].
 

Associations of IgG-2a with chemical compounds

  • In vitamin A-deficient rats the production of anti-TT IgG2b was severely impaired, with little change in either IgG1 or IgG2a [12].
  • Antigen-specific inhibition of ongoing murine IgE responses. II. Inhibition of IgE responses induced by treatment with glutaraldehyde-modified allergens is paralleled by reciprocal increases in IgG2a synthesis [20].
  • Cyclosporin A (CyA) administration, after transplantation, totally suppressed IgG1, IgG2a, IgG2b, and IgG2c EXA, and inhibited IgM EXA production, but failed to overcome rejection [22].
  • Furthermore, it was demonstrated that soluble mediators released after mast cell activation either by compound 48/80, or by IgE, or IgG2a-dependent reaction had the same effect as intact mast cells [21].
  • The molybdate-stabilized nonactivated rat liver glucocorticoid-receptor complex (Mr approximately 300,000) was immunoadsorbed on cyanogen bromide-activated Sepharose 4B to which a monoclonal IgG 2a antibody directed against the activated rat glucocorticoid receptor (Mr approximately 94,000) had been coupled [23].
 

Physical interactions of IgG-2a

  • Based on the present work and on previous results we conclude that IgG2a interacts with a receptor binding complexed IgG only (Fc gamma RII), IgG2b binds to a different receptor which appears to bind monomeric ligand as well (Fc gamma RI), while IgG1 seems to interact with both types of receptor [24].
 

Regulatory relationships of IgG-2a

 

Other interactions of IgG-2a

  • Partial depletion of CD4+ T cells markedly reduces IFN-gamma secretion without a major effect on the production of IL-10 and parasite-specific IgG2a Abs [26].
  • When given serially for 3 weeks, the incidence and severity of CIA, in addition to anti-CII IgG2a and splenic IL-6 and IFN-gamma production, were all significantly reduced [27].
  • After infection, males had higher Th1 immune responses (i.e., IgG2a, IFNgamma, and IL-2) than females; in contrast, Th2 immune responses (i.e., IgG1, IL-4, and IL-10) were similar between the sexes [28].
  • IgG1 and IgG2a anti-CII antibody levels were significantly greater in rats given 10 and 50 microg rIL-18 doses than controls. rIL-18 significantly increased levels of proinflammatory cytokines [interferon (IFN)-gamma, IL-2, tumour necrosis factor (TNF)-alpha and IL-6] produced by splenocyte cultures [27].
  • METHODS: Murine CTLA4Ig was made by joining two polymerase chain reaction products, the extracellular portion of CTLA4 and the Fc portion of IgG2a [29].
 

Analytical, diagnostic and therapeutic context of IgG-2a

  • By enzyme-linked immunosorbent assay, the paw tissue of these polyarthritic rats was shown to contain anticollagen IgG, the principal subclass being IgG2a, with minor amounts of IgG2b [30].
  • Fc receptors for rat IgG subclasses (IgG2a, IgG2c, and IgG1) were studied on rat eosinophils by rosette formation with erythrocytes coated with monoclonal immunoglobulin (Ig) or anti-Ig antisera in a reverse assay [31].
  • Adoptive transfer into naive recipients of purified IgM, IgG2b, or IgG2c, but not IgG1 or IgG2a EXA, induced xenograft rejection in a complement-dependent manner [22].
  • The abrogation of well established murine IgE responses that is elicited after treatment with OVA-POL (i) is potent (97%), (ii) is long lived, and (iii) reflects reciprocal regulation of Ag-specific IgE and IgG2a responses in vivo [20].
  • The cell supernatants of one particular IgG2a-producing clone (IPL Sm1) as well as ascitic fluids induced by this clone revealed anti-S. mansoni activity detected by immunofluorescence on schistosoma sections [32].

References

  1. CD28-B7 blockade prevents the development of experimental autoimmune glomerulonephritis. Reynolds, J., Tam, F.W., Chandraker, A., Smith, J., Karkar, A.M., Cross, J., Peach, R., Sayegh, M.H., Pusey, C.D. J. Clin. Invest. (2000) [Pubmed]
  2. Distinctive roles of neutrophils and monocytes in anti-thy-1 nephritis. Westerhuis, R., van Straaten, S.C., van Dixhoorn, M.G., van Rooijen, N., Verhagen, N.A., Dijkstra, C.D., de Heer, E., Daha, M.R. Am. J. Pathol. (2000) [Pubmed]
  3. Autoantibodies to the laminin P1 fragment in HgCl2-induced membranous glomerulopathy. Aten, J., Veninga, A., Coers, W., Sonnenberg, A., Timpl, R., Claessen, N., van Eendenburg, J.D., de Heer, E., Weening, J.J. Am. J. Pathol. (1995) [Pubmed]
  4. Immune response to Schistosoma mansoni infections in inbred rats. VII. Resistance is contingent on OX-8(+)-regulated high affinity IL-2 receptor-bearing W3/25+ lymphocytes but not on IL-4-dependent cells. Phillips, S.M., Perrin, P.J., Tung, A.S., Lin, J.J., Diamantstein, T., Galal, N. J. Immunol. (1991) [Pubmed]
  5. Analysis of T and B cell epitopes of the Schistosoma mansoni P28 antigen in the rat model by using synthetic peptides. Auriault, C., Gras-Masse, H., Wolowczuk, I., Pierce, R.J., Balloul, J.M., Neyrinck, J.L., Drobecq, H., Tartar, A., Capron, A. J. Immunol. (1988) [Pubmed]
  6. An anti-idiotype vaccine against experimental schistosomiasis. Grzych, J.M., Capron, M., Lambert, P.H., Dissous, C., Torres, S., Capron, A. Nature (1985) [Pubmed]
  7. Human HLA-DR beta gene hypervariable region homology in the biobreeding BB rat: selection of the diabetic-resistant subline as a rheumatoid arthritis research tool to characterize the immunopathologic response to human type II collagen. Watson, W.C., Thompson, J.P., Terato, K., Cremer, M.A., Kang, A.H. J. Exp. Med. (1990) [Pubmed]
  8. Specificity of fc receptors for IgG2a, IgG1/IgG2b, and IgE on rat macrophages. Boltz-Nitulescu, G., Bazin, H., Spiegelberg, H.L. J. Exp. Med. (1981) [Pubmed]
  9. Defects in antigen-specific immune tolerance in continuous B cell lines from autoimmune mice. Brooks, M.S., Aldo-Benson, M. J. Clin. Invest. (1986) [Pubmed]
  10. Production and characterization of N-terminally and C-terminally directed monoclonal antibodies against pancreatic glucagon. Gregor, M., Riecken, E.O. Gastroenterology (1985) [Pubmed]
  11. Ginseng treatment reduces bacterial load and lung pathology in chronic Pseudomonas aeruginosa pneumonia in rats. Song, Z., Johansen, H.K., Faber, V., Moser, C., Kharazmi, A., Rygaard, J., Høiby, N. Antimicrob. Agents Chemother. (1997) [Pubmed]
  12. Vitamin A status and immunoglobulin G subclasses in rats immunized with tetanus toxoid. Kinoshita, M., Ross, A.C. FASEB J. (1993) [Pubmed]
  13. Effect of intraperitoneal injection volume and antibody protein dose on the pharmacokinetics of intraperitoneally administered IgG2a kappa murine monoclonal antibody in the rat. Barrett, J.S., Wagner, J.G., Fisher, S.J., Wahl, R.L. Cancer Res. (1991) [Pubmed]
  14. Effect of myeloma IgE injections on passive and active cutaneous anaphylaxis in rats. Spiegelberg, H.L., Canning, K.M., Scheetz, M., Koppel, G., Chiller, J.M. J. Immunol. (1986) [Pubmed]
  15. Natural killer cell depletion fails to influence initial CD4 T cell commitment in vivo in exogenous antigen-stimulated cytokine and antibody responses. Wang, M., Ellison, C.A., Gartner, J.G., HayGlass, K.T. J. Immunol. (1998) [Pubmed]
  16. Endogenous glucocorticoids play a positive regulatory role in the anti-keyhole limpet hemocyanin in vivo antibody response. Fleshner, M., Deak, T., Nguyen, K.T., Watkins, L.R., Maier, S.F. J. Immunol. (2001) [Pubmed]
  17. Monoclonal antibodies against the rat liver glucocorticoid receptor. Okret, S., Wikström, A.C., Wrange, O., Andersson, B., Gustafsson, J.A. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  18. Potentiation by interleukin 2 of Burkitt's lymphoma therapy with anti-pan B (anti-CD19) monoclonal antibodies in a mouse xenotransplantation model. Vuist, W.M., v Buitenen, F., de Rie, M.A., Hekman, A., Rümke, P., Melief, C.J. Cancer Res. (1989) [Pubmed]
  19. In vitro killing of S. mansoni schistosomula by eosinophils from infected rats: role of cytophilic antibodies. Capron, M., Torpier, G., Capron, A. J. Immunol. (1979) [Pubmed]
  20. Antigen-specific inhibition of ongoing murine IgE responses. II. Inhibition of IgE responses induced by treatment with glutaraldehyde-modified allergens is paralleled by reciprocal increases in IgG2a synthesis. Hayglass, K.T., Stefura, W.P. J. Immunol. (1991) [Pubmed]
  21. Rat mast cell-eosinophil interaction in antibody-dependent eosinophil cytotoxicity to Schistosoma mansoni schistosomula. Capron, M., Rousseaux, J., Mazingue, C., Bazin, H., Capron, A. J. Immunol. (1978) [Pubmed]
  22. Complement-fixing elicited antibodies are a major component in the pathogenesis of xenograft rejection. Miyatake, T., Sato, K., Takigami, K., Koyamada, N., Hancock, W.W., Bazin, H., Latinne, D., Bach, F.H., Soares, M.P. J. Immunol. (1998) [Pubmed]
  23. The molybdate-stabilized nonactivated glucocorticoid receptor contains a dimer of Mr 90,000 non-hormone-binding protein. Denis, M., Wikström, A.C., Gustafsson, J.A. J. Biol. Chem. (1987) [Pubmed]
  24. Rat IgG subclasses mediating binding and phagocytosis of target cells by homologous macrophages. Miklós, K., Tolnay, M., Bazin, H., Medgyesi, G.A. Mol. Immunol. (1993) [Pubmed]
  25. Antisense oligonucleotides to interleukin-4 regulate IgE and IgG2a production by spleen cells from Nippostrongylus brasiliensis-infected rats. Benbernou, N., Matsiota-Bernard, P., Guenounou, M. Eur. J. Immunol. (1993) [Pubmed]
  26. Experimental African trypanosomiasis: a subset of pathogenic, IFN-gamma-producing, MHC class II-restricted CD4+ T cells mediates early mortality in highly susceptible mice. Shi, M., Wei, G., Pan, W., Tabel, H. J. Immunol. (2006) [Pubmed]
  27. The roles of interleukin-18 in collagen-induced arthritis in the BB rat. Ye, X.J., Tang, B., Ma, Z., Kang, A.H., Myers, L.K., Cremer, M.A. Clin. Exp. Immunol. (2004) [Pubmed]
  28. Sex differences in immune responses and viral shedding following Seoul virus infection in Norway rats. Klein, S.L., Bird, B.H., Glass, G.E. Am. J. Trop. Med. Hyg. (2001) [Pubmed]
  29. Prolonged xenograft survival of islets infected with small doses of adenovirus expressing CTLA4Ig. Feng, S., Quickel, R.R., Hollister-Lock, J., McLeod, M., Bonner-Weir, S., Mulligan, R.C., Weir, G.C. Transplantation (1999) [Pubmed]
  30. Type II collagen-induced arthritis. Studies with purified anticollagen immunoglobulin. Kerwar, S.S., Englert, M.E., McReynolds, R.A., Landes, M.J., Lloyd, J.M., Oronsky, A.L., Wilson, F.J. Arthritis Rheum. (1983) [Pubmed]
  31. Fc gamma receptors on rat eosinophils: isotype-dependent cell activation. Khalife, J., Capron, M., Grzych, J.M., Bazin, H., Capron, A. J. Immunol. (1985) [Pubmed]
  32. In vitro and in vivo effector function of rat IgG2a monoclonal anti-S. mansoni antibodies. Grzych, J.M., Capron, M., Bazin, H., Capron, A. J. Immunol. (1982) [Pubmed]
 
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