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

Richard K.S. Loh, Haifa H. Jabara, Clement L. Ren, Shu Man Fu, Donata Vercelli, Raif S. Geha

Research output: Contribution to journalArticle

14 Scopus citations

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 ε germline transcription in B cells stimulated with IL-4, but strongly inhibited induction of Sμ Sε 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.

Original languageEnglish (US)
Pages (from-to)99-106
Number of pages8
JournalImmunology Letters
Volume45
Issue number1-2
DOIs
StatePublished - Feb 1995
Externally publishedYes

Keywords

  • CD40
  • CD45
  • IgE synthesis
  • Isotype switching

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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