FDC-specific functions of p55TNFR and IKK2 in the development of FDC networks and of antibody responses

TitleFDC-specific functions of p55TNFR and IKK2 in the development of FDC networks and of antibody responses
Publication TypeJournal Article
Year of Publication2006
AuthorsVictoratos, P, Lagnel J, Tzima S, Alimzhanov MB, Rajewsky K, Pasparakis M, Kollias G
JournalImmunity
Volume24
Issue1
Pages66-77
Abstract

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.

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