A better understanding of the pathophysiological role of Langerhans cells (LC) in atopic diseases is dictated by the characterization of the structures involved in immunoglobulin (IgE)-binding on their cell surface. We previously reported that human LC express the high affinity receptor for IgE (Fc∈RI), as well as the low affinity receptor for IgE (Fc∈RII/CD23). In the present study, we document the presence of a third IgE-binding structure on human LC, the IgE-binding protein (∈BP), an endogenous soluble β-galactoside binding lectin. Immunohistochemical studies performed on normal human skin revealed an anti-∈BP reactivity in the cytoplasm of keratinocytes and in that of acinous cells of eccrine sweat glands. ∈BP was also found on the cell surface of LC, as shown by anti-∈BP/anti-CD1a double labeling and flow cytometric analysis. Anti-∈BP binding to the surface of LC was completely abolished by preincubation with lactose and restored by addition of recombinant human ∈BP, indicating that ∈BP binds to LC surface by virtue of its lectin property. Immunoblot analysis of anti-∈BP-reactive material in keratinocytes and purified LC disclosed a protein with an apparent molecular weight of 33,000 consistent with ∈BP. Interestingly, mRNA transcripts for ∈BP were detected only in keratinocytes but not in purified LC isolated from normal skin. ∈BP was found to be released in culture supernatants of keratinocytes. Incubation of LC with these supernatants resulted in ∈BP-binding to LC surface via protein-carbohydrate interaction. Most importantly, we could show that binding of human myeloma IgE to LC was inhibited by ∈BP. In contrast, neuraminidase-treated human myeloma IgE binds to LC only in the presence of ∈BP. In situ binding studies revealed that keratinocytes, although containing ∈BP intracytoplasmatically, failed to exhibit any IgE-binding properties. Collectively, our results suggest that human keratinocytes produce the β-galactoside-binding lectin ∈BP, which subsequently binds to the surface of LC where it is functional in modulating their binding capacity for IgE glycoforms.
|Original language||English (US)|
|Number of pages||9|
|Journal||Journal of Experimental Medicine|
|State||Published - Sep 1 1993|
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