Distinct cell-specific control of autoimmunity and infection by FcgammaRIIb.
FcgammaRIIb is an inhibitory Fc receptor expressed on B cells and myeloid cells. It is important in controlling responses to infection, and reduced expression or function predisposes to autoimmunity. To determine if increased expression of FcgammaRIIb can modulate these processes, we created transgenic mice overexpressing FcgammaRIIb on B cells or macrophages. Overexpression of FcgammaRIIb on B cells reduced the immunoglobulin G component of T-dependent immune responses, led to early resolution of collagen-induced arthritis (CIA), and reduced spontaneous systemic lupus erythematosus (SLE). In contrast, overexpression on macrophages had no effect on immune responses, CIA, or SLE but increased mortality after Streptococcus pneumoniae infection. These results help define the role of FcgammaRIIb in immune responses, demonstrate the contrasting roles played by FcgammaRIIb on B cells and macrophages in the control of infection and autoimmunity, and emphasize the therapeutic potential for modulation of FcgammaRIIb expression on B cells in inflammatory and autoimmune disease.
Brownlie
Rebecca J
RJ
Cambridge Institute for Medical Research and the Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 2OY, England, UK.
Lawlor
Kate E
KE
Niederer
Heather A
HA
Cutler
Antony J
AJ
Xiang
Zou
Z
Clatworthy
Menna R
MR
Floto
R Andres
RA
Greaves
David R
DR
Lyons
Paul A
PA
Smith
Kenneth G C
KG
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D001169:Arthritis, Experimental; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology; D051940:B7-2 Antigen / Q000276:immunology; D001424:Bacterial Infections; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007239:Infections / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D010766:Phosphorylation; D017452:Receptors, IgG / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D019076:Transgenes
D015703:Antigens, CD; D051940:B7-2 Antigen; C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D017452:Receptors, IgG; D048049:Extracellular Signal-Regulated MAP Kinases