eLife 7, e35074 (2018)

Mature naive B cells express surface IgM and IgD as BCRs, yet the distinct role of IgD has remained unknown. In eLife, Zikherman and colleagues show that IgD increases the dynamic range of BCR signaling in vivo but restrains the generation of antibodies by autoreactive B cells. They use reporter mice with IgM-only or IgD-only B cells that express a Nur77-eGFP reporter as a ‘readout’ of BCR signaling in vivo. IgM-only B cells show stronger signaling than that of IgD-only B cells in response to endogenous self antigen. Such self-reactive IgM-only B cells differentiate into short-lived plasma cells, whereas IgD-only B cells are less sensitive to antigen despite expressing more surface BCR molecules per cell. This difference in sensitivity might explain why wild-type IgMloIgDhi B cells can capture endogenous antigen but fail to spontaneously become autoantibody-secreting cells.