Defective B-cell tolerance in New Zealand black mice. Fc receptor-independence of resistance to low-epitope-density tolerogens

Trinitrophenyl (TNP) human gamma-globulin with low-epitope-density tolerizes B cells from normal BDF1 mice in a Fc gamma receptor-dependent manner but does not tolerize B cells from preautoimmune NZB mice. In order to investigate the relationships between tolerance induction and epitope density independently of Fc gamma receptor function in these two strains, TNP conjugates of two additional thymic-independent tolerogenic carriers, D-glutamic acid-D-lysine (D-GL) and carboxymethyl cellulose (CMC), were tested. A brief pulse with low-epitope-density conjugates such as TNP4.4-D-GL rendered unfractionated or T-cell-depleted spleen cells from BDF1 but not NZB mice tolerant in a hapten-specific manner. Spleen cells from NZB mice, however, were susceptible to tolerization with TNP13.5-D-GL. NZB mice were also resistant to tolerance induction in vivo with TNP5.5-D-GL, TNP3-CMC, and TNP6-CMC, all of which tolerize BDF1 mice in vivo. Both strains were tolerized with TNP13.5-D-GL and TNP13-CMC in vivo. NZB mice were also significantly less susceptible to tolerance induction with TNP3-CMC when TNP-Ficoll was substituted for TNP Brucella abortus as the challenge antigen. These findings militate against the possibility that an Fc gamma receptor defect is the principal mechanism of resistance of NZB B cells to tolerance induction with-low-epitope density conjugates.