Synergistic Induction of Interferon α through TLR-3 and TLR-9 Agonists Identifies CD21 as Interferon α Receptor for the B Cell Response

Maternal antibodies inhibit seroconversion and the generation of measles virus (mev)-specific antibodies (both neutralizing and non-neutralizing antibodies) after vaccination whereas t cell responses are usually unaffected. the lack of seroconversion leaves individuals susceptible to vaccine-preventable infections. inhibition of antibody secretion is due to the inhibition of b cells through a cross-link of the b cell receptor with the inhibitory fcγiib receptor (cd32) by maternal antibody/vaccine complexes. here,we demonstrate that a combination of tlr-3 and tlr-9 agonists induces synergistically higher levels of type i interferon in vitro and in vivo than either agonist alone. the synergistic action of tlr-3 and tlr-9 agonists is based on a feedback loop through the interferon receptor. finally,we have identified cd21 as a potential receptor for interferon α on b cells which contributes to interferon α-mediated activation of b cells in the presence of maternal antibodies. the combination leads to complete restoration of b cell and antibody responses after immunization in the presence of inhibitory mev-specific igg. the strong stimulatory action of type i interferon is due to the fact that type i interferon uses not only the interferon receptor but also cd21 as a functional receptor for b cell activation. © 2013 kim,niewiesk.