B cell tolerance induced by polymeric antigens. II. Effects of tolerance on hapten‐binding lymphocyte levels in primary and secondaryantibody responses

Abstract

Tolerogenic doses of hapten [2,4-dinitrophenyl (DNP)]-coupled type 3 pneumococcal polysaccharide (DNP-lys_2.5−S3) totally abolished the anti-DNP rosetteforming cell (RFC) response to primary immunization with DNP-hemocyanin in mice, while lightly substituted antigen (DNP-lys_0.6−S3) had little effect. Both antigens suppressed secondary anti-DNP RFC responses to DNP-KLH. Limiting doses of DNP-lys-S3 preferentially suppressed antibody-secreting cell levels, and had less effect on RFC. DNP-lys_2.5−S3 was 500—1000-fold more potent in “blockading” primary RFC in vitro than DNP-lys_0.6−S3, whereas both antigens were equally effective in blocking secondary RFC. These results suggest that the sensitivity of primed B lymphocytes to inactivation by DNP-lys-S3 is related to their high avidity for antigen. Furthermore, this appears to be largely due to a high density of immunoglobulin receptors on primed cells, since the affinitiesof primary and secondary RFC for monovalent hapten were indistinguishable. Treatment of primarily immunized mice with DNP-lys_2.5−S3 2 h before assay abolished 90 % of RFC. Therefore, the reduction in RFC levels in tolerant mice may be due to cellular blockade by persisting tolerogen. However, it seems unlikely that simple blockade of antigen-reactive cells is the sole mechanism operative in this system.