Cellular basis of persistent tolerance induced by an aggregate free heterologous immunoglobulin.

Attempts were made to break the tolerance of lymph node B cells to deaggregated human gamma globulin. Using allotype-congenic mice, lymph node cells from virgin or tolerant (5 mg) CBA/Igb donors were transferred tonormal CBA/Iga recipients and the proportion of responding donor B cells estimated 1 and 13 days later. The response of the non-tolerant virgin cells diminished with time but was still detectable at 13 days whereas the response of the tolerant cells was tenfold lower than normal cells at day 1 and was not detectable at 13 days. This functional deletion of tolerant cells was not reversed by enzymatic stripping of the immuno-globulin receptors before transfer, nor by removing T cells-which might have had a suppressor action. In other experiments Igb mice were thymectomized or left as controls at various times before tolerance induction. Lymph node cells from these mice were transferred, together with non-tolerant Iga cells, to irradiated recipients. The cell from tolerant thymectomized donors strongly suppressed the response of non-tolerant cells, whereas the tolerant control cells showed no suppressor activity. It is considered that B-cell tolerance can be maintained by something other than receptor blockade, or active suppression-although the latter can arise in some circumstances.