Specific suppression of hybridoma immunoglobulin secretion by hapten-conjugated mouse IgG: a model of B-cell tolerance.

In an effort to establish a model system for studying B-cell tolerance, the effects of hapten-conjugated isologous mouse IgG on the secretion of antibody by a mouse hybridoma cell line were studied. The hybridoma cell line 35-12 (HC) secretes IgM antibody to the hapten dinitrophenyl (DNP). After HC cells are injected intraperitoneally into BALB/c mice, the cells initially undergo a marked reduction in the proportion of PFC/10(6) followed by a return of PFC to pretransfer levels by 7-10 days. Hapten-conjugated mouse IgG (DNP-MGG), which induces tolerance to DNP in normal mouse B cells, also induces suppression of HC PFC when administered within the first 2 days after the transfer. Administration of tolerogen either 2 days before injection of HC or after the PFC response has returned to preinjection levels fails to give suppression. Suppression is dose dependent and hapten specific since immunogenic hapten-carrier conjugates (e.g., DNP-KLH, DNP-Ficoll) and fluorescein-MGG are not suppressive. T cells may not be required for suppression since hybridoma cells inoculated into nude mice are also suppressed by DNP-MGG. These results suggest that hybridoma cells undergo a change from nonsecreting to secreting cells during in vivo growth and that administration of tolerogen during the nonsecreting stage inhibits antibody secretion.