The in vivo function of a noncanonical TRAF2-binding domain in the C-terminus of CD40 in driving B-cell growth and differentiation

Li Fan Lu, Cory L. Ahonen, Evan F. Lind, Vanitha S. Raman, W. James Cook, G. Li Lin, Randolph J. Noelle

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The recruitment of tumor necrosis factor receptor-associated factors (TRAFs) 1, 2, 3, 5, and 6 to the CD40 cytoplasmic tail upon CD40 trimerization results in downstream signaling events that ultimately lead to CD40-dependent, thymus-dependent (TD) humoral immune responses. Previously, we have shown signaling through the C-terminal tail of CD40 in the absence of canonical TRAF-binding sites is capable of signaling through an alternative TRAF2-binding site. Here, we demonstrate that B cells from mice harboring CD40 with only the C-terminal tail can activate both canonical and noncanonical NFκB signaling pathways. Moreover, while lacking germinal center formation, several hallmarks of humoral immune responses including clonal B-cell activation/expansion, antibody isotype switching, and affinity maturation remain normal. This study demonstrates a new functional domain in CD40 that controls critical aspects of B-cell immunity in an in vivo setting.

Original languageEnglish (US)
Pages (from-to)193-200
Number of pages8
JournalBlood
Volume110
Issue number1
DOIs
StatePublished - Jul 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Lu, L. F., Ahonen, C. L., Lind, E. F., Raman, V. S., Cook, W. J., Lin, G. L., & Noelle, R. J. (2007). The in vivo function of a noncanonical TRAF2-binding domain in the C-terminus of CD40 in driving B-cell growth and differentiation. Blood, 110(1), 193-200. https://doi.org/10.1182/blood-2006-07-038414