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

13 Citations (Scopus)

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 - 1995
Externally publishedYes

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Immunoglobulin Class Switching
Protein Tyrosine Phosphatases
Protein-Tyrosine Kinases
Immunoglobulin E
B-Lymphocytes
Interleukin-4
Phosphoric Monoester Hydrolases
src-Family Kinases
Avidin
T-Cell Antigen Receptor
Genetic Recombination
Signal Transduction
Monoclonal Antibodies
Phosphorylation
T-Lymphocytes
Polymerase Chain Reaction

Keywords

  • CD40
  • CD45
  • IgE synthesis
  • Isotype switching

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Role of protein tyrosine kinases and phosphatases in isotype switching : crosslinking CD45 to CD40 inhibits IgE isotype switching in human B cells. / Loh, Richard K S; Jabara, Haifa H.; Ren, Clement L.; Fu, Shu Man; Vercelli, Donata; Geha, Raif S.

In: Immunology Letters, Vol. 45, No. 1-2, 1995, p. 99-106.

Research output: Contribution to journalArticle

Loh, Richard K S ; Jabara, Haifa H. ; Ren, Clement L. ; Fu, Shu Man ; Vercelli, Donata ; Geha, Raif S. / Role of protein tyrosine kinases and phosphatases in isotype switching : crosslinking CD45 to CD40 inhibits IgE isotype switching in human B cells. In: Immunology Letters. 1995 ; Vol. 45, No. 1-2. pp. 99-106.
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