ROLE OF PROTEIN-TYROSINE KINASES AND PHOSPHATASES IN ISOTYPE SWITCHING - CROSS-LINKING CD45 TO CD40 INHIBITS IGE ISOTYPE SWITCHING IN HUMANB-CELLS

Protein tyrosine kinases and protein tyrosine phosphatases play an imp ortant role in the transduction of signals via antigen receptors in T and B cells, and in CD40-dependent B-cell activation. To examine the r ole of tyrosine kinases and phosphatases in B-cell isotype switching, we examined the effects of the engagement of the transmembrane phospha tase CD45 on the synthesis of IgE induced by IL-4 and anti-CD40 monocl onal antibody (mAb). Crosslinking CD45 to CD40 using biotinylated mAbs and avidin strongly inhibited CD40-mediated IgE synthesis in IL-4-tre ated human B cells. CD40/CD45 crosslinking did not affect epsilon germ line transcription in B cells stimulated with IL-4, but strongly inhib ited induction of S mu/S epsilon switch recombination as detected by a nested primer polymerase chain reaction assay. The B-cell src-type ty rosine kinase lyn, which is activated following CD40 engagement, is a potential target for the effects of CD45 observed in our experiments, because CD45/CD40 crosslinking resulted in the inhibition of CD40-medi ated lyn phosphorylation and activation. These results suggest an impo rtant role for protein tyrosine kinases and phosphatases in CD40mediat ed induction of isotype switching to IgE.