Kinetics and drug sensitivity of the anti-hapten and anti-carrier IgG1 and IgG2 antibody production in guinea pigs.

Abstract

The influence of the hapten-protein ratio on the induction and kinetics of specific IgG1 and IgG2 anti-hapten and anti-carrier antibody synthesis, and the sensitivity of these reactions to cyclophosphamide (CY) and 6-mercaptopurine (6-MP), were studied following immunization with two different dinitrophenylated bovine gamma-globulin (DNP20-BGG and DNP47-BGG) conjugates in Freund's complete adjuvant (FCA) and drug treatment over the first 7 days after antigen injection. The DNP- and BGG-specific IgG1 and IgG2 serum antibody concentrations were determined weekly. Treatment by CY resulted in a complete suppression of the primary IgG1 and IgG2 anti-BGG antibody response, both in the DNP20-BGG and DNP47-BGG immunized guinea pigs. The anti-DNP response was completely suppressed only up to day 14 (DNP20-BGG immunized group) or day 21. This was followed by an increase that was significantly greater in the DNP20-BGG than in the DNP47-BGG immunized animals. The secondary IgG1 anti-BGG immune response induced by an injection of 1 mg BGG on day 86, was uninfluenced in animals immunized with DNP20-BGG but stimulated in the other group treated with DNP47-BGG. The IgG2 was completely suppressed in both groups. 6-MP, known to be less immunosuppressive in guinea pigs, led to very similar results. The finding that in animals immunized with DNP47-BGG the primary anti-BGG IgG2 antibody synthesis was uninfluenced by 6-MP, but the development of a memory was suppressed, would suggest that the primary antibody response and immunological memory are either separate mechanisms or have different sensitivities to 6-MP.