The antigen presentation function of bone marrow-derived mast cells is spatiotemporally restricted to a subset expressing high levels of cell surface FcεRI and MHC II
1 Department of Allergy and Immunology, IgE Therapeutics, Inc., San Diego, CA, USA
2 Agriculture Biotechnology Research Center, Academia Sinica, Taipei, Taiwan
3 Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA, USA
4 Department of Dermatology, University of California-Davis, Sacramento, CA, USA
5 Department of Molecular Biology, The Scripps Research Institute, San Diego, CA, USA
BMC Immunology 2010, 11:34 doi:10.1186/1471-2172-11-34Published: 30 June 2010
At present, it is highly controversial whether pure mast cells can serve as antigen presenting cells, and it is not known whether the capacity of antigen presenting function is temporally restricted to a particular subset of differentiated mast cells. Evidence is presented for a novel surface FcεRIhi , MHC II +, and c-kit + pure mast cell subset, temporally restricted as antigen-presenting cells in the immune axis of T-cell activation.
Bone marrow-derived mast cells (BMMC) cultured in the presence of IL-3 for three weeks are pure mast cells based on surface expression of lineage-specific marker, c-kit and FcεRI. Herein we present the first demonstration that approximately 98.7% c-kit + and FcεRI expressing BMMC, further depleted of any contaminated professional antigen-presenting cells, are still fully capable of presenting antigens, i.e., OVA protein, OVA peptide, and IgE-TNP-OVA, to OVA peptide-specific T-cell hybridomas. Notably, IgE-dependent antigen presentation is more efficient compared to that resulting from direct antigen uptake. Importantly, we present the novel finding that only surface FcεRIhi mast cells, also expressing surface MHC II exhibited antigen-presenting function. In contrast, surface FcεRIlo mast cells without expressing surface MHC II were not capable of antigen presentation. Interestingly, the antigen-presenting function of BMMC was irrevocably lost during the third and fourth week in IL-3 or SCF containing cultures.
This is the first observation to attribute a spatiotemporally restricted antigen-presenting function to a subset of three-week old pure BMMC expressing both high levels of surface FcεRI and surface MHC II. We propose that mast cells play an important role in immune deviating and/or sustaining the activation of infiltrating CD4 T-cells, and modulating T-cell mediated allergic inflammation via its flexibility to present antigens and antigen-IgE complexes.