Ontogeny of human IgE-expressing B cells and plasma cells

BackgroundIgE-expressing (IgE(+)) plasma cells (PCs) provide a continuous source of allergen-specific IgE that is central to allergic responses. The extreme sparsity of IgE(+) cells in vivo has confined their study almost entirely to mouse models. ObjectiveTo characterize the development pathway of human IgE(+) PCs and to determine the ontogeny of human IgE(+) PCs. MethodsTo generate human IgE(+) cells, we cultured tonsil B cells with IL-4 and anti-CD40. Using FACS and RT-PCR, we examined the phenotype of generated IgE(+) cells, the capacity of tonsil B-cell subsets to generate IgE(+) PCs and the class switching pathways involved. ResultsWe have identified three phenotypic stages of IgE(+) PC development pathway, namely (i) IgE(+)germinal centre (GC)-like B cells, (ii) IgE(+)PC-like plasmablasts' and (iii) IgE(+)PCs. The same phenotypic stages were also observed for IgG1(+) cells. Total tonsil B cells give rise to IgE(+) PCs by direct and sequential switching, whereas the isolated GC B-cell fraction, the main source of IgE(+) PCs, generates IgE(+) PCs by sequential switching. PC differentiation of IgE(+) cells is accompanied by the down-regulation of surface expression of the short form of membrane IgE (mIgE(S)), which is homologous to mouse mIgE, and the up-regulation of the long form of mIgE (mIgE(L)), which is associated with an enhanced B-cell survival and expressed in humans, but not in mice. ConclusionGeneration of IgE(+) PCs from tonsil GC B cells occurs mainly via sequential switching from IgG. The mIgE(L)/mIgE(S) ratio may be implicated in survival of IgE(+) B cells during PC differentiation and allergic disease.