A GPI-linked isoform of the IgD receptor regulates resting B cell activation.

The induction of a humoral response depends upon efficient cross-linking by antigen of surface immunoglobulin on primary B lymphocytes. We demonstrate here the presence of a glycosylphosphatidylinositol-linked isoform of membrane IgD (mIgD) receptors on murine resting B cells. This subset was constitutively localized to cell membrane raft microdomains. Its stimulation resulted in the activation of cAMP-dependent signaling pathways, which integrated with signals derived from the transmembrane mIgD receptors. This, in turn, provided a mechanism by which the activation status of the target cells could be variably regulated. Thus, by partitioning receptor activity, preimmune B cells can moderate the extent to which they are activated, depending upon the strength of the antigenic stimulus.