IgG2a-mediated enhancement of antibody and T cell responses and its relation to inhibitory and activating Fc gamma receptors.
A number of studies in experimental animal models point to an important role of Fc gamma Rs in autoimmunity and allergy. In this study, we investigate how the production of IgG, an early step in the chain of events leading to inflammation, is regulated by activating and inhibitory Fc gamma Rs. IgG Abs are known to feedback-enhance Ab responses to soluble Ags, and this effect requires activating Fc gamma Rs. To test proliferation of Th cells, mice were adoptively transferred with CD4(+) T cells expressing a transgenic OVA-specific TCR before immunization with IgG2a anti-2,4,6-trinitrophenyl (TNP) plus OVA-TNP or with OVA-TNP alone. IgG2a induced a significant increase in OVA-specific T cell numbers, which preceded the OVA-specific Ab response and was dependent on the Fc gamma chain. The role of the inhibitory Fc gamma RIIB in Ab responses was studied in mice lacking this receptor. Although IgG2a enhanced primary Ab responses, development of germinal centers, and immunological memory in wild-type mice, enhancement was markedly stronger in Fc gamma RIIB(-/-) mice. The presented data are compatible with the hypothesis that the mechanism behind IgG2a-mediated up-regulation of Ab responses involves increased Ag presentation to CD4(+) T cells by Fc gamma R(+) APCs. Our observations also illustrate the intricate immunoregulatory role of IgG Abs. On the one hand, they enhance Ab responses via activating Fc gamma Rs, and on the other hand, they set an upper limit for the same Ab response via Fc gamma RIIB.
Getahun
Andrew
A
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Dahlström
Jörgen
J
Wernersson
Sara
S
Heyman
Birgitta
B
D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D015536:Down-Regulation / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D018984:Epitopes, T-Lymphocyte; C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D008024:Ligands; D017452:Receptors, IgG