Human Basophils Express the Glycosylphosphatidylinositol-Anchored Low-Affinity IgG Receptor FcγRIIIB (CD16B)

Abstract

Basophils express not only high-affinity IgE receptors, but also low-affinity IgG receptors. Which, among these receptors, are expressed by human basophils is poorly known. Low-affinity IgG receptors comprise CD32 (FcγRIIA, FcγRIIB, and FcγRIIC) and CD16 (FcγRIIIA and FcγRIIIB). FcγRIIA, FcγRIIC, and FcγRIIIA are activating receptors, FcγRIIB are inhibitory receptors, FcγRIIIB are GPI-anchored receptors whose function is poorly understood. Basophils were reported to express FcγRII, but not FcγRIII. We aimed at further identifying basophil IgG receptors. Basophils from normal donors and from patients suffering from an allergic skin disease (atopic dermatitis), allergic respiratory diseases (allergic rhinitis and asthma), or a nonallergic skin disease (chronic urticaria) were examined. We found that normal basophils contain FcγRIII transcripts and express FcγRIIIB, but not FcγRIIIA, which were detected on 24–81% basophils from normal donors and on 12–100% basophils from patients. Noticeably, the proportion of FcγRIIIB+ basophils was significantly lower in atopic dermatitis patients than in other subjects. This decreased FcγRIII expression was not correlated with an activated phenotype of basophils in atopic dermatitis patients, although FcγRIIIB expression was down-regulated upon basophil activation by anti-IgE. Our results challenge the two dogmas 1) that basophils do not express FcγRIII and 2) that FcγRIIIB is exclusively expressed by neutrophils. They suggest that a proportion of basophils may be lost during enrichment procedures in which FcγRIII+ cells are discarded by negative sorting using anti-CD16 Abs. They unravel an unexpected complexity of IgG receptors susceptible to modulate basophil activation. They identify a novel systemic alteration in atopic dermatitis.

Fcγ Receptors Inhibit Mouse and Human Basophil Activation

“…3A). As in our previous works (22), we failed to activate human basophils by aggregating FcgRIIIB with F(ab9) 2 fragments of FcgRIII-specific mAb 3G8, whether aggregated with F(ab9) 2 goat anti-mouse or not (Supplemental Fig. 3B), even if cells were primed with IL-3 (data not shown).…”

“…IgG receptors were described long ago on human basophils (18) and identified as FcgRIIA, FcgRIIB (19,20), and FcgRIIIB (22). FcgR were also observed on mouse basophils (25), but not identified.…”

“…FcgRIIA are single-chain ITAM-containing activating receptors, whereas FcgRIIB are singlechain ITIM-containing inhibitory receptors (21). Human basophils also express minute amounts of the GPI-anchored low-affinity IgG receptor FcgRIIIB (22), whose biological properties are unclear. They express neither FcgRIIIA nor high-affinity IgG receptors (FcgRI) and, unlike in human mast cells (23), FcgRI were not inducible by IFN-g in human basophils (24).…”

Mouse and human neutrophils induce anaphylaxis

“…Human neutrophils, indeed, do not express FcγRI, FcεRI, or FcγRIIIA. They, however, express the GPI-anchored FcγRIIIB (31,32). FcγRIIA, but not FcγRIIIB, could bind IC made with mouse IgG1, IgG2a, or IgG2b ( Figure 8B).…”

Induced Expression of FcγRIIIa (CD16a) on CD4+ T Cells Triggers Generation of IFN-γhigh Subset

“…7B). The confirmed sequence covered exons 4 and 5 ( phils also successfully amplified an appropriate size a 242-bp DNA fragment (not shown) (37).…”