Role of protein tyrosine kinases and phosphatases in isotype switching: crosslinking CD45 to CD40 inhibits IgE isotype switching in human B cells

Immunology Letters
R LohR S Geha

Abstract

Protein tyrosine kinases and protein tyrosine phosphatases play an important role in the transduction of signals via antigen receptors in T and B cells, and in CD40-dependent B-cell activation. To examine the role of tyrosine kinases and phosphatases in B-cell isotype switching, we examined the effects of the engagement of the transmembrane phosphatase CD45 on the synthesis of IgE induced by IL-4 and anti-CD40 monoclonal antibody (mAb). Crosslinking CD45 to CD40 using biotinylated mAbs and avidin strongly inhibited CD40-mediated IgE synthesis in IL-4-treated human B cells. CD40/CD45 crosslinking did not affect epsilon germline transcription in B cells stimulated with IL-4, but strongly inhibited induction of S mu/S epsilon switch recombination as detected by a nested primer polymerase chain reaction assay. The B-cell src-type tyrosine 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-mediated lyn phosphorylation and activation. These results suggest an important role for protein tyrosine kinases and phosphatases in CD40-mediated induction of isotype switching to IgE.

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Citations

Jun 10, 1998·Springer Seminars in Immunopathology·N RameshR S Geha
Feb 11, 2000·The Journal of Allergy and Clinical Immunology·L B Bacharier, R S Geha
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·T MorioR S Geha
Aug 26, 1998·Proceedings of the National Academy of Sciences of the United States of America·P Scheipers, H Reiser
Mar 31, 2005·Seminars in Cell & Developmental Biology·Daniela De ZioFrancesco Cecconi
Sep 2, 2003·Nature Reviews. Immunology·Raif S GehaScott R Brodeur
Feb 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cheng ZhouKe Zhang

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