Signal transduction via the human b lymphocyte antigen cd22 results in a potent b cell stimulatory signal and the association of cd22 with a complex of effector molecules

The interactions between lymphocyte counter receptors are thought to stabilize the physical associations between cells and transduce signals that modulate antigen driven responses.CD22 is a B lymphocyte specific membrane protein that functions as an adhesion molecule. While CD22 mediates both homo- and heierotypic-cell adhesion the consequences of direci engagement of CD22 on B-cell function are unknown Within the cytoplasmic tail ot'CU22 are 6 precisely space tyrosme which are arranged in a pattern which is consistent with a motif termed the antigen recepior homology l (ARH1) motif- We sought to examine the biochemical processes and functional effects of CD22 signaling. Engagement of CD22 with a monoclonal antibody (HR22.7) that blocks the binding of CD22 to its ligatid results in rapid lyrosine phosphorylation and increased association of CD22 with p53/56lyn kinase, p85Pl-3 kinase, and p72syk kinase. Synthetic peptides that span various regions of the intracelhjlar portion of CD22 were used to map the potential kinase binding sites. All three kinases associated with the tyrosine phosphorylated peptide that spans tyrosine ammo acid residues 822 and 842. In an attempt to examine the functional effects of CD22 signal transduction we used various monoclonal antibodies (mAb) directed against the extra cytoplasmic domain of CD22 When CD22 was crosslinked with the mAb that blocked me ability of CD22 to bind its ligand (HB22.7) il resulted in a significant increase in B cell proliferation when compared to crosslinking with the non blocking mAb (CD22.5). In addition HB22.7 co-stimulated B-cell proliferation with either ami-lgM, imerleukin (IL)-, IL-, or CD40 and triggered predominantly IgM secretion with IL-2.ln contrast, CD22.5 poorly co-stimulated in duplicate experiments. The functional differences between the two antibodies likely results trom differing abilities to trigger downstream signaling events. Significant differences in CD22 tyrosine phosphorylation and the recruitment of p53/S6lyn and SH-Pl PIC were observed. Besides their role in B cell stimulation, CD22/CD22L interactions may also regulate T cell proliferation since inhibition of CD22/CD22L engagement with HB22 7 impaired T cell piohferation in a co-stimulation assay whereas CD22.5 had no effect Thus, CD22/CD22L interactions result in CD22 tyrosine phosphorylation , assemblage of a signal transduction complex which results in augmented H cell function.