In this work, we studied the expression and function of CD22 in murine B cells. CD22 has been previously characterized as an activation marker of mature B lymphocytes. However, we found that CD22 is expressed early during the ontogeny of B cells in the bone marrow and spleen, and was found on B cells isolated from all the different lymphoid compartments. We also found that B cells stimulated through the B-cell antigen receptor (BCR), CD38 and CD40, upregulated CD22 expression to maximal levels within 24 h after stimulation, but that the levels of CD22 declined at later times (48 and 72 h). CD22 is rapidly phosphorylated after BCR signal transduction, and is believed to downregulate B-cell activation. In this study, we did not detect CD22 phosphorylation in activated B cells after CD38 or CD40 cross-linking, even though CD22 was clearly phosphorylated in the BCR-stimulated B cells. Consistent with this, we found no evidence of physical association between CD38 or CD40 and CD22 in B cells. The lack of association or phosphorylation of CD22 induced by CD38 and CD40 crosslinking indicates that CD22 may not downregulate the activation induced by these two molecules. [ABSTRACT FROM AUTHOR]