CpG oligodeoxynucleotides induce cyclooxygenase‐2 and prostaglandin synthesis in human B lymphocytes: Implications for antibody production and innate immunity.

Abstract

Many chronic inflammatory diseases are characterized by infiltrates of B cells and plasma cells coupled with high prostaglandin (PG) levels. B cells were not previously thought to express cyclooxygenase‐2 (Cox‐2) and PGs. Interest in CpG oligodeoxynucleotides (ODN) is fueled by clinical trials that show CpG ODN enhance antibody production and act as adjuvants. Since antibodies play a key role in fighting infections, it is important to understand how CpG ODN affect human B cells and influence antibody production. We recently demonstrated that activated human B cells highly express Cox‐2 and that Cox‐2 activity is crucial for optimal antibody production (J. Immunology, 177:7811, 2006). Herein, we tested the hypothesis that CpG ODNs induce human B cell Cox‐2 and that Cox‐2 activity is important for optimal antibody production. Exposure of human B lymphocytes to synthetic CpG ODN sequences increased steady‐state Cox‐2 mRNA levels and induced Cox‐2 protein. Importantly, CpG‐induced IgM and IgG production was attenuated following inhibition of Cox‐2 activity by selective drug inhibitors. CpG motifs therefore enhance antibody production by directly stimulating B cells and by inducing Cox‐2. These findings support the concept that drugs that attenuate Cox‐2 activity can reduce optimal antibody response to adjuvants/vaccination.