Antiviral B cell memory in the absence of mature follicular dendritic cellnetworks and classical germinal centers in TNFR1(-/-) mice

TNFR1(-/-) mice have been shown to lack networks of mature follicular dendr itic cells (FDCs) and they do not form germinal centers. With nonreplicatin g Ags, IgG titers were inefficiently induced and not maintained, In this st udy, the neutralizing Ab response and the establishment of B cell memory in TNFR1(-/-) mice after infection with vesicular stomatitis virus (VSV) were analyzed histologically and functionally. Immunization with VSV-derived pr otein Ags without adjuvant induced only IgM but no IgG Abs in TNFR1(-/-) mi ce, whereas VSV glycoprotein emulsified in CFA or IFA induced IgM and IgG r esponses that were short-lived and of moderate titer. However, infection wi th live VSV induced excellent neutralizing IgM and IgG responses in TNFR1(- /-) mice, and adoptively transferable B cell memory was generated and persi sted for more than 300 days. In contrast, IgG levels and Ab-forming cells i n the bone marrow declined within 300 days by 90-95% compared with controls . These findings suggest that 1) increased Ag dose and time of Ag availabil ity can substitute for FDC-stored Ab-complexed Ag in the induction of effic ient IgG responses in TNFR1(-/-) mice devoid of classical germinal centers; 2) the induction and maintenance of adoptively transferable B cell memory can occur in the absence of Ag bound to mature FDCs; and 3) the long-term m aintenance of elevated IgG titers is largely dependent on FDC-associated pe rsisting Ag, However, about 5-10% of the Ab production remained in the abse nce of detectable persisting Ag in TNFR1(-/-) mice, probably either due to immature FDCs being partially functional and/or due to long-lived plasma ce lls.