Intrinsic properties of germinal center‐derived B cells promote their enhanced class switching to IgE

Background Research on the origins and development of human IgE‐expressing (IgE+) cells is required for understanding the pathogenesis of allergy and asthma. These studies have been thwarted by the rarity of IgE+ cells in vivo and the low frequency of class switch recombination (CSR) to IgE ex vivo. To determine the main source of IgE+ cells, we investigated the relation between the phenotypic composition of tonsil B cells and the CSR to IgE ex vivo. Methods Human tonsil B cells were analyzed by flow cytometry (FACS) and cultured with IL‐4 and anti‐CD40 to induce CSR to IgE. Naïve, germinal center (GC), early GC (eGC), and memory tonsil B cells were isolated by FACS, and their capacities for IL‐4 and anti‐CD40 signaling, cell proliferation, and de novo class switching to IgE were analyzed by RT‐PCR and FACS. Results B cells from different tonsils exhibited varying capacities for CSR to IgE ex vivo. This was correlated with the percentage of eGC B cells in the tonsil at the outset of the culture. Despite relatively poor cell viability, eGC and GC B‐cell cultures produced the highest yields of IgE+ cells compared to naïve and memory B‐cell cultures. The main factors accounting for this result were the strength of IL‐4R and CD40 signaling and relative rates of cell proliferation. Conclusions This study shows that the maturation state of tonsil B cells determines their capacity to undergo class switching to IgE ex vivo, with the GC‐derived B cells yielding the highest percentage of IgE+ cells.