BCR ligation antagonizes the IL-21 enhancement of anti-CD40/IL-4 plasma cell differentiation and IgE production found in low density human B cell cultures

We sought to discover the mechanisms explaining increased IgE production seen at low cell densities when IL-21 is added to human B cell cultures activated with anti-CD40 and IL-4. When cells were cultured in the absence of BCR ligation, qPCR demonstrated dramatic increases in mRNA for the plasma cell transcription factors BLIMP1 and XBP1. Furthermore, a majority of viable cells expressed high levels of CD38 while losing expression of surface IgD. In contrast, in the presence of BCR stimulation, both the XBP1 mRNA levels and CD38 cell surface expression were markedly reduced, and a large population of cells retained IgD expression, indicating reduced plasma cell differentiation. IgE levels were reduced in the BCR stimulated cultures by 90%, while IgG4 levels remained unchanged. In summary, IL-21 enhances IgE production at low densities through stimulating cell division and plasma cell differentiation and this activity is reduced upon BCR cross-linking.