Inhibition of cyclooxygenase-2 activity impairs antibody production in human B cells and in mice infected with vaccinia virus (84.8)

Abstract

Abstract Generation of protective humoral immune responses against vaccines depends on optimal production of antibodies by B lymphocytes. Non-steroidal anti-inflammatory drugs (NSAIDs) are used to curb undesirable symptoms of vaccination, including pain, fever and swelling. We previously demonstrated in B cells that cyclooxygenase-2 (Cox-2) is induced in response to both T-dependent and T-independent stimuli, including the TLR9 ligand CpG DNA, and that Cox-2 is crucial for antibody production. Expression of plasma cell transcriptional regulatory factors, including Blimp-1 and Xbp-1, were dependent on Cox-2 activity. Significantly fewer antibody secreting plasma cell precursors were generated in the presence of Cox-2 selective inhibitors, indicating that Cox-2 is essential for human B cell terminal differentiation. Cox-2 selective inhibitors were administered in vivo to determine the role of Cox-2 in a humoral immune response to live infection with vaccinia virus. Mice chronically treated with Cox-2 selective inhibitors produced less viral neutralizing IgG following live virus infection. Inhibition of Cox-2 resulted in a reduced frequency of IFN-γ producing T cells, indicating that T cell priming of B cells was attenuated. These data support the idea that impaired humoral immunity in the absence of Cox-2 activity can be dependent on both B cells and T cells and that the use of Cox-2 selective inhibitors have the potential to dampen humoral immunity to live virus infection and vaccines.