Generation of anti-NZB red blood cell antibody-forming plasma cells from bone marrow cultures of syngeneic and allogeneic mice: functional modulation of helper T-cell subsets in autosensitization.

An in vitro anti-NZB red blood cell (RBC) autoantibody-forming system was developed by culturing young (antiglobulin negative) or old (antiglobulin positive) NZB mouse bone marrow cells in the presence of young or old NZB thymocyte homogenates (or RNA thymus extracts) and young NZB-RBC. Using young NZB bone marrow cells, the greatest number of autoantibody forming cells were seen following stimulation with a mixture of young and old thymocyte homogenates (TH). A higher response was seen with old NZB bone marrow cells stimulated by old NZB thymocyte homogenates and RBC. Phenol-extracted thymic RNA retained activity when added to bone marrow culture containing NZB-RBC. Thymus RNA from 9 to 10 days old NZB mice had no activity although their bone marrow cells responded well to stimulation by young and old thymic RNA together with RBC. By analysing results obtained using T-cells enriched for helper and suppressor activities, we have concluded that abrogation of self-tolerance in mice is due to the appearance of functionally modulated helper T-cell subsets and to imbalance between helper and suppressor T cells.