11/16/2023 0 Comments Prodeus iggOur findings demonstrate that the dual receptor usage of type I interferon receptor and CD21 is crucial for B cell activation in the presence of maternal antibodies. The strong stimulation by interferon is due to the previously unappreciated role of CD21 as functional receptor for interferon alpha. The best induction of type I interferon was accomplished by a combination of known activators of interferon secretion (a combination of TLR-3 and TLR-9 agonists). We also found that induction of large amounts of type I interferon restores the neutralizing antibody response in the presence of maternal antibodies. Here, we show that this cross-link results in impaired B cell activation and proliferation which is correlated with diminished antibody responses. This interference is caused by a vaccine/maternal antibody complex which links the B cell receptor to the inhibitory CD32 molecule. Maternal antibodies provide protection against infection with pathogens early in life but also interfere with vaccination. 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. The combination leads to complete restoration of B cell and antibody responses after immunization in the presence of inhibitory MeV-specific IgG. 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 synergistic action of TLR-3 and TLR-9 agonists is based on a feedback loop through the interferon receptor. 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. 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. The lack of seroconversion leaves individuals susceptible to vaccine-preventable infections. 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.
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