CD72, a B cell surface protein of the C-type lectin superfamily, recruits t
he tyrosine phosphatase SHP-1 through its ITIM motif(s). Using CD72-deficie
nt (CD72(-/-)) mice, we demonstrate that CD72 is a nonredundant regulator o
f B cell development. In the bone marrow of CD72(-/-) mice, there was a red
uction in the number of mature recirculating B cells and an accumulation of
pre-B cells. In the periphery of CD72(-/-) mice, there were fewer mature B
-2 cells and more B-l cells. In addition, CD72 is a negative regulator of B
cell activation, as CD72(-/-) B cells were hyperproliferative in response
to various stimuli and showed enhanced kinetics in their intracellular Ca2 response following IgM cross-linking.