Unique monoclonal antibodies define expression of Fc gamma RI on macrophages and mast cell lines and demonstrate heterogeneity among subcutaneous and other dendritic cells.
The mouse Fc gamma RI is one of the most fundamentally important FcRs. It participates in different stages of immunity, being a low affinity receptor for T-independent IgG3 and yet a high affinity receptor for IgG2a, the product of a Th1 immune response. However, analysis of this receptor has been difficult due largely to the failure to generate specific Abs to this FcR. We have made use of the polymorphic differences between BALB/c and NOD/Lt mice to generate mAb specific for the Fc gamma RI of BALB/c and the majority of in-bred mouse strains. Three different mAb were obtained that detected Fc gamma RI encoded by the more common Fcgr1(a) and Fcgr1(b) alleles, and although they identified different epitopes, none inhibited the binding of IgG to Fc gamma RI. When bound to Fc gamma RI, these mAb induced calcium mobilization upon cross-linking. Several novel observations were made of the cellular distribution of Fc gamma RI. Resting and IFN-gamma-induced macrophages expressed Fc gamma RI as well as mast cell lines. Both bone marrow-derived and freshly isolated dendritic cells from spleen and lymph nodes expressed Fc gamma RI. A class of DC, uniquely found in s.c. lymph nodes, expressed the highest level of Fc gamma RI and also high levels of MHC class II, DEC205, CD40, and CD86, with a low level of CD8 alpha, corresponding to the phenotype for Langerhans-derived DC, which are highly active in Ag processing. Thus, in addition to any role in effector functions, Fc gamma RI on APC may act as a link between innate and adaptive immunities by binding and mediating the uptake of T-independent immune complexes for presentation, thereby assisting in the development of T-dependent immune responses.
Tan
Peck S
PS
Austin Research Institute, Austin and Repatriation Medical Center, Heidelberg, Victoria, Australia.
Gavin
Amanda L
AL
Barnes
Nadine
N
Sears
Duane W
DW
Vremec
David
D
Shortman
Ken
K
Amigorena
Sebastian
S
Mottram
Patricia L
PL
Hogarth
P Mark
PM
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis* / Q000096:biosynthesis / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000032:analysis* / Q000096:biosynthesis / Q000378:metabolism; D000915:Antibody Affinity / Q000235:genetics; D000916:Antibody Diversity / Q000235:genetics; D000918:Antibody Specificity / Q000235:genetics; D001666:Binding Sites, Antibody / Q000235:genetics; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D016466:CHO Cells; D020013:Calcium Signaling / Q000235:genetics / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D006224:Cricetinae; D003432:Cross-Linking Reagents / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018604:Epitope Mapping; D006801:Humans; D007739:L Cells; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D016688:Mice, Inbred NOD; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D016513:Mice, SCID; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012513:Sarcoma, Experimental / Q000276:immunology; D012867:Skin / Q000166:cytology / Q000276:immunology*; D013045:Species Specificity; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D011961:Receptors, Fc; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins