Ontogeny of human IgE‐expressing B cells and plasma cells

Background IgE‐expressing (IgE + ) plasma cells ( PC s) 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 characterize the development pathway of human IgE + PC s and to determine the ontogeny of human IgE + PC s. Methods To generate human IgE + cells, we cultured tonsil B cells with IL ‐4 and anti‐ CD 40. Using FACS and RT ‐ PCR , we examined the phenotype of generated IgE + cells, the capacity of tonsil B‐cell subsets to generate IgE + PC s and the class switching pathways involved. Results We 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 + PC s. The same phenotypic stages were also observed for IgG1 + cells. Total tonsil B cells give rise to IgE + PC s by direct and sequential switching, whereas the isolated GC B‐cell fraction, the main source of IgE + PC s, generates IgE + PC s 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. Conclusion Generation of IgE + PC s 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.