Linker proteins function as molecular scaffolds to Localize enzymes with su
bstrates. In B cells, B cell Linker protein (BLNK) Links the B cell recepto
r (BCR)activated Syk kinase to the phosphoinositide and mitogen-activated k
inase pathways. To examine the in vivo role of BLNK, mice deficient in BLNK
were generated. B cell development in BLNK-/- mice was blocked at the tran
sition from B220(+) CD43(+) progenitor B to B220(+) CD43(-) precursor B cel
ls. Only a small percentage of immunoglobulin M++ (IgM(++)), but not mature
IgM(lo)lgD(hi), B cells were detected in the periphery. Hence, BLNK is an
essential component of BCR signaling pathways and is required to promote B
cell development.