Studies of immune responses in mice prone to autoimmune disorders: I. Heterogeneity of the affinities of antihapten antibodies produced by NZB,NZW, and related strains of mice

Mice of the NZB and NZW strains and their F₁ hybrid produce antihapten plaque-forming cell (PFC) responses to T-dependent antigens (trinitrophenylated bovine gamma globulin and dansylated keyhole limpet hemocyanin) which are of unusually restricted heterogeneity of affinity, are relatively lacking in low-affinity PFC, and are of relatively high average affinity. Since some low-affinity PFC are present in NZB mice early after immunization, the results suggest a particularly marked down-regulation of low-affinity antibody production by these strains. The non-autoimmune-prone F₁ hybrid (NZB × CBA) produces a typical heterogeneous response containing a high proportion of low-affinity PFC. Thus, the tendency to down-regulate low-affinity PFC is not inherited as a simple Mendelian dominant trait. The response of NZB mice to T-independent antigens does not show the same restricted heterogeneity of affinity. In fact, late after injections of trinitrophenylated Ficoll, NZB mice tend to have more heterogeneous responses than nonautoimmune-prone BALB/c mice in which a marked down-regulation of high-affinity antibody-producing PFC is seen. The possible relationship between these unusual features of the immune response of NZB and some related strains and their tendency to develop autoimmune disease is discussed.