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 (mIgE_S ), which is homologous to mouse mIgE, and up-regulation of the long-form of mIgE (mIgE_L ), 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 mIgE_L/mIgE_S 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.