The CD40-TRAF6 axis controls affinity maturation and the generation of long-lived plasma cells

Cory L. Ahonen, Eric M. Manning, Loren D. Erickson, Brian P. O'Connor, Evan F. Lind, Steven S. Pullen, Marilyn R. Kehry, Randolph J. Noelle

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

Affinity maturation of the immune response and the generation of long-lived bone marrow (BM) plasma cells are hallmarks of CD40-dependent, thymus-dependent (TD) humoral immunity. Through disruption of the tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)-binding site within the CD40 cytoplasmic domain, we selectively ablated affinity maturation and the generation of plasma cells after immunization. Mutagenesis of both the TRAF6 and TRAF2-TRAF3 sites was essential for arresting germinal center formation in response to immunization. CD40-induced B cell proliferation and early immunoglobulin production occurred even when all TRAF sites were ablated. These studies show that specific CD40-TRAF associations control well defined aspects of humoral immunity. In addition, they define the roles that TRAF-dependent and TRAF-independent pathways play in regulating antigen-driven B cell differentiation.

Original languageEnglish (US)
Pages (from-to)451-456
Number of pages6
JournalNature Immunology
Volume3
Issue number5
DOIs
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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