Prostaglandin E2 production is enhanced in mice genetically selected to produce high affinity antibody responses.

Spleen cells from mice selectively bred to produce high affinity antibody responses to protein antigens (HI) had reduced responses to both T and B cell mitogens when compared to those from mice selectively bred to produce low affinity (LO) responses. The reduced response by spleen cells from HI mice was partially reversed by the addition of indomethacin in vitro. Spleen adherent cells from HI mice had increased production of prostaglandin E2 when compared to those from LO mice. In addition, spleen adherent cells from mice which fail to show affinity maturation not only produced lower amounts of PGE2 than those from HI mice but also a decreased proportion of spleen cells adhered to plastic in these mice. To test the possibility that the increased PGE2 production in HI mice was responsible for the production of high affinity antibodies, indomethacin was administered in vivo and resulted in a significant reduction in antibody affinity. The possibility that PGE2 production may control the balance between the TH1 and TH2 cells of Mosmann and Coffman is discussed.