Kinase MEKK1 is required for CD40-dependent activation of the kinases Jnk and p38, germinal center formation, B cell proliferation and antibody production

Nat Immunol. 2007 Jan;8(1):57-63. doi: 10.1038/ni1421. Epub 2006 Dec 3.


Mice lacking activity of the kinase MEKK1 ('Map3k1(deltaKD)' mice) have defective activation of the kinase Jnk and increased production of T helper type 2 cytokines after T cell receptor ligation. Here we show that Map3k1(deltaKD) mice had defective germinal center formation and diminished production of antibodies recognizing thymus-dependent antigens. Those defects were B cell intrinsic, as MEKK1 was necessary for CD40-mediated activation of the kinases Jnk and p38 and transcription factor c-Jun, as well as for expression of cyclin D2 and activation-induced deaminase. MEKK1 was recruited to CD40 and adaptor molecule TRAF2 after CD40 ligation, and Map3k1(deltaKD) B cells were hypoproliferative after CD40 stimulation. Our data emphasize that MEKK1 is an essential component of signaling cascades needed for thymus-dependent antigen-induced B cell proliferation and antibody production.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / immunology*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • CD40 Antigens / metabolism*
  • Germinal Center / immunology*
  • Lymphocyte Activation / immunology*
  • MAP Kinase Kinase 4 / metabolism*
  • MAP Kinase Kinase Kinase 1 / genetics
  • MAP Kinase Kinase Kinase 1 / metabolism*
  • Mice
  • Signal Transduction / immunology
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • CD40 Antigens
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 1
  • MAP Kinase Kinase 4