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PMID: 11967542 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Nature immunology ·Vol. 3 ·No. 5 ·2002-05-00 ·Pages 451-6

Ahonen C, Manning E, Erickson LD, O'Connor B, Lind EF, Pullen SS, Kehry MR, Noelle RJ

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.

MeSH Terms
Animals Antibody Formation/immunology Base Sequence CD40 Antigens/immunology CD40 Ligand/immunology Cell Differentiation/immunology Enzyme-Linked Immunosorbent Assay Germinal Center/immunology Immunoglobulin G/analysis,biosynthesis Immunoglobulin M/analysis,biosynthesis Immunohistochemistry Mice Mice, Transgenic Molecular Sequence Data Plasma Cells/cytology,immunology Proteins/immunology Receptors, IgE/analysis,biosynthesis Signal Transduction/immunology TNF Receptor-Associated Factor 6
Chemicals
CD40 Antigens Immunoglobulin G Immunoglobulin M Proteins Receptors, IgE TNF Receptor-Associated Factor 6 CD40 Ligand
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Ahonen Cory
Department of Microbiology and Immunology, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, NH 03756, USA.
Manning Eric
Erickson Loren D
O'Connor Brian
Lind Evan F
Pullen Steven S
Kehry Marilyn R
Noelle Randolph J
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2908
DOI
10.1038/ni792
Published
2002-05-00
Epub
2002-00-22
Pages
451-6
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC2834483
Subset
IM
Grants
NCI NIH HHS · CA 23108 · United States
NIAID NIH HHS · R01 AI026296-09 · United States
NCI NIH HHS · P30 CA023108-315667 · United States
NIAID NIH HHS · R37 AI026296 · United States
NCI NIH HHS · P30 CA023108 · United States
NIAID NIH HHS · AI26296 · United States
NIAID NIH HHS · R01 AI026296 · United States
External Links
PubMed source DOI: 10.1038/ni792 PMC Full Text View journal details
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