The CD40-TRAF6 axis controls affinity maturation and the generation of long-lived plasma cells.
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.
Ahonen
Cory
C
Department of Microbiology and Immunology, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, NH 03756, USA.
Manning
Eric
E
Erickson
Loren D
LD
O'Connor
Brian
B
Lind
Evan F
EF
Pullen
Steven S
SS
Kehry
Marilyn R
MR
Noelle
Randolph J
RJ
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001483:Base Sequence; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018858:Germinal Center / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000032:analysis / Q000096:biosynthesis; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology; D011506:Proteins / Q000276:immunology*; D017455:Receptors, IgE / Q000032:analysis / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology; D048029:TNF Receptor-Associated Factor 6
D019013:CD40 Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011506:Proteins; D017455:Receptors, IgE; D048029:TNF Receptor-Associated Factor 6; D023201:CD40 Ligand