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

Ewen Gallagher, Thomas Enzler, Atsushi Matsuzawa, Amy Anzelon-Mills, Dennis Otero, Ryan Holzer, Edith Janssen, Min Gao, Michael Karin

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)

Abstract

Mice lacking activity of the kinase MEKK1 ('Map3k1ΔKD' 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 Map3k1ΔKD 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 Map3k1ΔKD 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.

Original languageEnglish
Pages (from-to)57-63
Number of pages7
JournalNature Immunology
Volume8
Issue number1
DOIs
Publication statusPublished - 2007 Jan
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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