The ontogeny of IgE forming cells

The origin and fate of IgE forming cells has commanded attention for more than 50 years largely because they drive allergic diseases that plague a third of the world’s most economically privileged populations. Ontogeny studies began in the early1980s with the expressed intent of locating these cells so that IgE production might be turned off at the source, at the level of the IgE forming B cell. They continue to the present day. The technological revolution at the turn of the last century neatly divides efforts. From the outset, IgE seemed unlike other isotypes. IgE forming cells did not appear to clone in germinal centers like other B cells, but to arise rapidly and transiently within gut after stimulation. Long-lived memory seemed to reside in the periphery, in spleen and bone marrow. Even those early ontogeny studies hinted at isotype switching. As the century turned, advances in flow cytometry and the creation of transgenic mice synergized to allow the reliable detection of vanishingly rare cells. New technologies allowed genetic analysis of even single cells. With resolution unimaginable 20 years before, IgE forming cells were found to arise from direct and indirect isotype switching, from IgM and IgG precursors, potentially in all organs, including thymus and perhaps any tissue exposed to allergen. Armed with new tools, future work may one day soon make good on the old vision of turning off IgE responses at their source, at the level of the IgE forming cell.