B cell tolerance induced by polymeric antigens. IV. Antigen-mediated inhibition of antibody-forming cells.

The role of antibody-forming cell (AFC) blockade in the genesis of hapten-specific tolerance induced by hapten (2,4-dinitrophenyl)-coupled pneumococcal polysaccharide (DNP-lys-S3) was investigated. Tolerizing doses of DNP-lys-S3 given to mice making antibodies to DNP-hemocyanin a day before assay markedly reduced numbers of detectable anti-DNP AFC. Furthermore, anti-DNP AFC were specifically inhibited by brief in vitro incubation with DNP-lys-S3, followed by extensive washing. This inhibition requires multivalent binding of tolerogen to immunoglobulin receptors on AFC, and appears to result from a decrease in the rate of antibody secretion per cell. A variety of data indicate that IgM AFC are more susceptible to blockade than IgG AFC, and the susceptibility of both cell types decreases with time after immunization. This probably reflects differences in the density and in the rate of loss of surface immunoglobulin receptors on IgM and IgG AFC and their immediate precursors. However, we conclude that under "conventional" tolerizing conditions, i.e. when tolerogen is given prior to immunogen, DNP-lys-S3 suppresses antibody formation primarily by inactivating DNP-specific precursor cells. AFC blockade is therefore probably only relevant in the suppression of (primary?) IgM responses by large doses of tolerogen. The relative importance of precursor inactivation and AFC blockade in tolerogenesis of IgM responses to T cell-independent antigens (such as S3) remains to be elucidated.