T-cell-dependent oscillations of IgM antibody affinity during the immune response to DNP-Dextran to low or high epitope density

Abstract

Anti-hapten IgM antibody response and affinity were evaluated by haemolytic plaque inhibition assay on spleen cells from mice immunized with 2,4, dinitrophenyl (DNP)1.3-Dextran or DNP13-Dextran. Regardless of epitope density, affinity was found to mature with time after immunization and to be characterized by rapid oscillations independent of changes in anti-hapten plaque-forming cell (PFC) response and antibody secretion rate. Injection of the lower epitope density immunogen not only elicited higher PFC responses and higher affinity antibodies but also induced more pronounced affinity oscillations mainly confined to the higher affinity PFC subpopulation. Immunization of athymic nude mice with DNP1.3-Dextran elicited PFC responses comparable to those observed in similarly immunized euthymic mice. However, affinity oscillations were drastically reduced in athymic mice and the restricted variation of antibody affinity observed shortly after immunization was followed by no oscillations in any of the affinity PFC subpopulations. Athymic mice did not produce high affinity PFC which account to a large extent for the affinity oscillations observed in euthymic mice. These findings demonstrate the important role of T cells in the appearance of rapid changes in IgM antibody affinity. The generation of T-cell-dependent oscillations of high affinity antibody-producing cell subpopulations is discussed in terms of interactions among cells and soluble factors involved in regulatory circuits of the immune network.