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

Abstract

BackgroundAt 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.ResultsBone 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.ConclusionsThis 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.

IL-33 promotes MHC class II expression in murine mast cells

“…However, we are not certain why prolonged IL-33 exposure is crucial to this process. IFN-g has been known to induce MHC class II protein in spleen-derived mast cells [35]. However, in our study prolonged treatment of BMMCs with IL-33 did not result in IFN-g secretion.…”

“…Previous studies reported that spleen-derived mast cells expressed MHC class II protein after stimulation by LPS and IFN-g [34]. Immature BMMCs reportedly expressed MHC class II protein and acquired antigen-presenting activity, which diminished after maturation [35]. In our experiments, mature BMMCs cultured for 4 weeks expressed MHC class II protein only very slightly (Fig.…”

Mast Cells as Critical Effectors of Host Immune Defense against Gram-negative Bacteria

“…The former subset of BMMCs (FcεRI hi /MHCII + ) is able to present antigens to T cells, whereas the latter subset (FcεRI lo /MHCII -) fails to present antigens. The authors also showed that the extended culture with IL-3 diminished the antigen presenting function of BMMCs [113]. Although these reports have indicated that mast cells are capable of initiating acquired immunity against invading microbes, the actual biological contribution of antigen presentation by mast cells remains mostly unknown.…”

“…A recent report has indicated that most of the mouse BMMCs expressing high levels of surface FcεRI concomitantly express abundant MHC class II on their cell surface, whereas most of the BMMCs with low levels of surface FcεRI expression exhibit little expression of MHC class II on their cell surface [113]. The former subset of BMMCs (FcεRI hi /MHCII + ) is able to present antigens to T cells, whereas the latter subset (FcεRI lo /MHCII -) fails to present antigens.…”

The history of the controversial relationship between mast cells and basophils

“…These mast cells were able to present antigen to effector T cells causing their activation, proliferation, and formation of an immunological synapse between the mast cell and the T cell. Very recently, the antigen-presenting function has been shown to be restricted to a subset of three-week old pure BMMCs expressing both high levels of surface FcRI and surface MHC class II [87]. Collectively, studies indicate that mast cells represent a rich source of co-stimulatory activity by expressing also molecules of the B7 family (ICOS-L, PD-L1, PD-L2, CD80, CD86), members of the TNF/TNF receptor families (OX40L, CD153, Fas, 4-1BB), CD28 and CD40 ligand [88,89].…”