Lupus-specific antiribonucleoprotein B cell tolerance in nonautoimmune mice is maintained by differentiation to B-1 and governed by B cell receptor signaling thresholds

Systemic lupus erythematosus is an autoimmune disease characterized by the presence of autoantibodies. One of the unique targets of the immune system in systemic Iupus erythematosus is Sm, a ribonucleoprotein present in all c ells. To understand the regulation of B cells specific to the Sm Ag in norm al mice, we have generated an Ig H chain transgenic mouse (2-12H Tg), 2-12H Tg mice produce B cells specific for the Sm that remain tolerant due to ig norance, We demonstrate here that anti Sm B cells of 2-12H Tg mice can diff erentiate into Sm-specific peritoneal B-l cells that remain tolerant. Diffe rentiation to D-I and tolerance are governed by the strength of B cell rece ptor signaling, since manipulations of the B cell receptor coreceptors CD19 and CD22 affect anti-Sm B cell differentiation and autoantibody production . These results suggest a differentiation scheme in which peripheral ignora nce to Sm is maintained in mice by the differentiation of anti-Sm B cells t o B-l cells that have increased activation thresholds. The Journal of Immun ology, 2001, 166: 2412-2419.