FDC-specific functions of p55TNFR and IKK2 in the development of FDC networks and of antibody responses.
The FDC-specific molecular signals required in the formation of FDC networks, B cell follicles, and germinal centers (GCs) have remained poorly understood. We used FDC-specific gene targeting to investigate the function of p55TNFR and IKK2 in lymphoid organ structure and function. Here we show that FDC-specific expression of p55TNFR is necessary and sufficient to promote FDC network and B cell follicle formation, restore the expression of CXCL13 and VCAM-1/ICAM-1 in FDCs, and lead to productive GCs. Notably, FDC-specific disruption of IKK2 does not affect formation of FDC networks. Yet, after antigen engagement or immune complex (IC) deposition, FDCs lacking IKK2 fail to upregulate VCAM-1 and ICAM-1, and GCs remain sterile. These findings demonstrate that IKK2-independent function of p55TNFR on FDCs is sufficient to support the development of FDC networks and GCs, while FDC-specific IKK2 is indispensable for the generation of efficient humoral immune responses.
Victoratos
Panayiotis
P
Institute of Immunology, Biomedical Sciences Research Center Al. Fleming, Vari 166-72, Greece.
Lagnel
Jacques
J
Tzima
Sotiria
S
Alimzhanov
Marat B
MB
Rajewsky
Klaus
K
Pasparakis
Manolis
M
Kollias
George
G
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D054382:Chemokine CXCL13; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D020566:Dendritic Cells, Follicular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018390:Gene Targeting; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D007074:Immunoglobulin G / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D017464:Receptors, Complement 3d / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
D015815:Cell Adhesion Molecules; D054382:Chemokine CXCL13; D018925:Chemokines; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D007074:Immunoglobulin G; D017464:Receptors, Complement 3d; D047888:Receptors, Tumor Necrosis Factor, Type I; D014157:Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse