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 Lind, Steven S. Pullen, Marilyn R. Kehry, Randolph J. Noelle

Research output: Contribution to journalArticle

108 Citations (Scopus)

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

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Humoral Immunity
Plasma Cells
Immunization
B-Lymphocyte Differentiation Antigens
TNF Receptor-Associated Factor 3
TNF Receptor-Associated Factor 2
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Germinal Center
Mutagenesis
Bone Marrow Cells
Thymus Gland
Immunoglobulins
B-Lymphocytes
Binding Sites
Cell Proliferation

ASJC Scopus subject areas

  • Immunology

Cite this

Ahonen, C. L., Manning, E. M., Erickson, L. D., O'Connor, B. P., Lind, E., Pullen, S. S., ... Noelle, R. J. (2002). The CD40-TRAF6 axis controls affinity maturation and the generation of long-lived plasma cells. Nature Immunology, 3(5), 451-456. https://doi.org/10.1038/ni792

The CD40-TRAF6 axis controls affinity maturation and the generation of long-lived plasma cells. / Ahonen, Cory L.; Manning, Eric M.; Erickson, Loren D.; O'Connor, Brian P.; Lind, Evan; Pullen, Steven S.; Kehry, Marilyn R.; Noelle, Randolph J.

In: Nature Immunology, Vol. 3, No. 5, 2002, p. 451-456.

Research output: Contribution to journalArticle

Ahonen, CL, Manning, EM, Erickson, LD, O'Connor, BP, Lind, E, Pullen, SS, Kehry, MR & Noelle, RJ 2002, 'The CD40-TRAF6 axis controls affinity maturation and the generation of long-lived plasma cells', Nature Immunology, vol. 3, no. 5, pp. 451-456. https://doi.org/10.1038/ni792
Ahonen CL, Manning EM, Erickson LD, O'Connor BP, Lind E, Pullen SS et al. The CD40-TRAF6 axis controls affinity maturation and the generation of long-lived plasma cells. Nature Immunology. 2002;3(5):451-456. https://doi.org/10.1038/ni792
Ahonen, Cory L. ; Manning, Eric M. ; Erickson, Loren D. ; O'Connor, Brian P. ; Lind, Evan ; Pullen, Steven S. ; Kehry, Marilyn R. ; Noelle, Randolph J. / The CD40-TRAF6 axis controls affinity maturation and the generation of long-lived plasma cells. In: Nature Immunology. 2002 ; Vol. 3, No. 5. pp. 451-456.
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