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

Panayiotis Victoratos, Jacques Lagnel, Sotiria Tzima, Marat B Alimzhanov, Klaus Rajewsky, Manolis Pasparakis, George Kollias

Institute of Immunology, Biomedical Sciences Research Center Al. Fleming, Vari 166-72, Greece.

Immunity 2006 Jan

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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.

Citation

Panayiotis Victoratos, Jacques Lagnel, Sotiria Tzima, Marat B Alimzhanov, Klaus Rajewsky, Manolis Pasparakis, George Kollias. FDC-specific functions of p55TNFR and IKK2 in the development of FDC networks and of antibody responses. Immunity. 2006 Jan;24(1):65-77