Selective activation of c-Jun kinase mitogen-activated protein kinase by CD40 on human B cells

J Biol Chem. 1995 Dec 22;270(51):30823-8. doi: 10.1074/jbc.270.51.30823.

Abstract

The B cell surface antigen receptor, surface IgM (sIgM), is involved in B cell activation and proliferation. CD40 is involved in regulating IgE production and B cell survival. Cross-linking of B cell sIgM activates the Ras/Raf/p42erk2 pathway. In contrast, ligation of CD40 by antibody or soluble gp39 (CD40 ligand) leads to activation of the c-Jun kinase (JNK)/stress-activated protein kinase pathway. JNK/stress-activated protein kinase activation correlated with the stimulation of MEK kinase activity. CD40 does not activate the p42erk2 pathway, and sIgM fails to regulate the JNK/stress-activated protein kinase pathway in B cells. Thus, two important cell surface receptors involved in controlling specific B cell response differentially regulate sequential protein kinase pathways involving different members of the mitogen-activated protein kinase family. Anti-CD40 also rescued B cell apoptosis induced by anti-IgM. CD40 ligation did not affect the sIgM stimulation of p42erk2 activity. Conversely, sIgM ligation did not influence CD40 stimulation of JNK/stress-activated protein kinase. These results suggest that independent, parallel protein kinase response pathways are involved in the integration of sIgM and CD40 control of B cell phenotype and function.

MeSH terms

  • Antibodies / pharmacology
  • Antigens, CD / physiology*
  • B-Lymphocytes / enzymology*
  • B-Lymphocytes / immunology
  • Burkitt Lymphoma
  • CD40 Antigens / physiology*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Line
  • Enzyme Activation
  • Humans
  • Immunoglobulin M / physiology
  • JNK Mitogen-Activated Protein Kinases
  • Kinetics
  • MAP Kinase Kinase Kinase 1*
  • Mitogen-Activated Protein Kinases*
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-raf
  • Receptors, Antigen, B-Cell / physiology
  • Recombinant Fusion Proteins / metabolism
  • Tumor Cells, Cultured
  • ras Proteins / metabolism

Substances

  • Antibodies
  • Antigens, CD
  • CD40 Antigens
  • Immunoglobulin M
  • Proto-Oncogene Proteins
  • Receptors, Antigen, B-Cell
  • Recombinant Fusion Proteins
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 1
  • MAP3K1 protein, human
  • ras Proteins