Distinct role of neonatal and adult monocytes in the regulation of the in vitro antigen-induced plaque-forming cell response in man.

Abstract

Mononuclear cells from human cord blood (CBMC) are able to mount an antigen-specific IgM plaque-forming cell (PFC) response after primary in vitro stimulation with the T cell-dependent antigen ovalbumin (OA). The antigen dose-response relationship for the induction of PFC in cultures of CBMC is represented by a bell-shaped curve comparable to that found for mononuclear cells from adult peripheral blood (adult PBMC). The dose of OA optimal for the induction of a response in cultures of CBMC consistently, however, is 100-fold lower than the antigen dose optimal for adult PBMC (0.03 microgram OA/ml vs 3.0 micrograms OA/ml). Results obtained from co-culture experiments in which semiallogeneic combinations of parental/neonatal lymphocytes and monocytes were stimulated with a variable dose of OA indicate that the adherent cell (AC) plays a pivotal role in the establishment of the optimum antigen dose. From experiments using antigen-pulsed AC, it was concluded that neonatal and adult AC differ in their antigen handling capacity. In the presence of the prostaglandin synthetase inhibitor indomethacin the antigen dose-response relationship for the induction of PFC in cultures of CBMC shifts to an "adult type" of curve. From pulsing experiments it emerges that indomethacin affects the interaction between antigen and monocytes. Indomethacin causes an enhancement of the expression of HLA-DR at the surface of neonatal as well as adult AC; this can be down regulated by the addition of prostaglandin E2 (PGE2). The addition of PGE2 to cultures of adult PBMC leads to a shift of the optimal antigen dose for induction of PFC toward lower concentrations. Although higher levels of PGE2 were measured in the supernatant of cultured neonatal AC compared with adult AC, it seems unlikely that this observation can explain the distinct antigen dose-response relationship for the induction of a PFC response in cultures of CBMC.