Ontogeny of Human IgE-expressing B Cells and Plasma Cells

BACKGROUND: IgE-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.OBJECTIVE: To characterise the development pathway of human IgE+ PCs and to determine the ontogeny of human IgE+ PCs.METHODS: To 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.RESULTS: We have identified three phenotypic stages of IgE+ PC development pathway, namely (i) IgE+ 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 down-regulation of surface expression of the short-form of membrane IgE (mIgES ), which is homologous to mouse mIgE, and up-regulation of the long-form of mIgE (mIgEL ), which is associated with enhanced B cell survival and expressed in humans, but not in mice.CONCLUSION: Generation of IgE+ PCs from tonsil GC B cells occurs mainly via sequential switching from IgG. The mIgEL/mIgES ratio may be implicated in survival of IgE+ B cells during PC differentiation and allergic disease. This article is protected by copyright. All rights reserved.