UNRESPONSIVENESS FOLLOWING IMMUNIZATION WITH THE T-CELL-INDEPENDENT ANTIGEN DEXTRAN B512 - CAN IT BE ABROGATED

The bacterial carbohydrate dextran B512 is a thymus-independent (TT) a ntigen and a poor immunogen. Humoral responses consist primarily of Ig M and no memory response is observed; rather, secondary responses to n ative dextran are similar to or suppressed compared with primary respo nses. However, immune responses to dextran can be enhanced. In this st udy we have used a protein-dextran conjugate that elicits a thymus-dep endent (TD) immune response against dextran. Furthermore, we used the potent adjuvant cholera toxin (CT) for the dextran immunizations. This enables us to re-evaluate the phenomenon of poor secondary response t o dextran and whether it can be abrogated. We show that native dextran -primed mice were not able to mount IgG anti-dextran antibody response s after repeated immunizations with the TD, protein-dextran conjugate. This was also apparent in the spleen, where almost no dextran-specifi c germinal centres were detected. However, the anti-protein antibody r esponse was normal in these mice, demonstrating that it is only the an ti-dextran-responding cells that are affected. The effect of CT adjuva nt on these events was also evaluated. CT enhanced the humoral IgM ant i-dextran responses as well as the splenic responses to dextran. But, the isotype profile was not altered, still no Ige was produced. In con trast, mice primed with the TD conjugate and repeatedly re-immunized w ith native, TI, dextran generated IgG anti-dextran responses. Our resu lts indicate that it is probable that the lack of proper costimulation in the initiation of the response to dextran causes the suppressed se condary dextran responses. Furthermore, these results suggest that TI and TD forms of dextran activate the same type of B cells, since TI, d extran-priming abrogated TD dextran IgG responses. The importance of t he priming event for the induction of a classical memory response to c arbohydrate antigens and the implications for vaccination strategies, are discussed.