Cutting edge: B cell antigen receptor signaling occurs outside lipid raftsin immature B cells

B cell Ag receptor (BCR) signaling changes dramatically during B cell devel opment, resulting in activation in mature B cells and apoptosis, receptor e diting, or anergy in immature Ei cells. BCR signaling in mature B cells was shown to be initiated by the translocation of the BCR into cholesterol- an d sphingolipid-enriched membrane microdomains that include the Src family k inase Lyn and exclude the phosphatase CD45. Subsequently the BCR is rapidly internalized into the cell. Here we show that the BCR in the immature B ce ll line, WEHI-231, does not translocate into lipid rafts following cross-li nking nor is the BCR rapidly internalized, The immature BCR initiates signa ling from outside lipid rafts as evidenced by the immediate induction of an array of phosphoproteins and subsequent apoptosis, The failure of the BCR in immature B cells to enter lipid rafts may Contribute to the dramatic dif ference in the outcome of signaling in mature and immature B cells.