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 characterize 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 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 ), which is homologous to mouse mIgE, and the up-regulation of the long form of mIgE (mIgE ), which is associated with an 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 /mIgE ratio may be implicated in survival of IgE B cells during PC differentiation and allergic disease.