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RI on Macrophages and Mast Cell Lines and Demonstrate Heterogeneity Among Subcutaneous and Other Dendritic Cells 1
* Austin Research Institute, Austin and Repatriation Medical Center, Heidelberg, Victoria, Australia;
The Scripps Research Institute, La Jolla, CA 92037;
Department of Biological Sciences, University of California, Santa Barbara, CA 93106;
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; and
¶ Institut Curie, Section de Recherche, Paris, France
The mouse Fc
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 FcRI of BALB/c and the majority of in-bred mouse strains. Three different mAb were obtained that detected FcRI encoded by the more common Fcgr1a and Fcgr1b alleles, and although they identified different epitopes, none inhibited the binding of IgG to FcRI. When bound to FcRI, these mAb induced calcium mobilization upon cross-linking. Several novel observations were made of the cellular distribution of FcRI. Resting and IFN--induced macrophages expressed FcRI as well as mast cell lines. Both bone marrow-derived and freshly isolated dendritic cells from spleen and lymph nodes expressed FcRI. A class of DC, uniquely found in s.c. lymph nodes, expressed the highest level of FcRI and also high levels of MHC class II, DEC205, CD40, and CD86, with a low level of CD8
, corresponding to the phenotype for Langerhans-derived DC, which are highly active in Ag processing. Thus, in addition to any role in effector functions, FcRI 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.
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