Transplantation of autoimmune potential. III. Immunological hyper-responsiveness and elevated endogenous spleen colony formation in lethally irradiated recipients of NZB bone marrow cells.

Our previous studies have demonstrated that NZB→DBA/2 bone marrow radiation chimeras spontaneously develop antinuclear auto-antibodies and immune complex renal disease. The present report describes the associated appearance in these chimeras of an NZB-like elevation in endogenous spleen colony formation and in hyper-responsiveness with regard both to sheep erythrocyte immunization and to spleen cell stimulation by T-cell mitogens. These observations would suggest that the hyperproliferative properties of the stem cells and immunocytes of the NZB reflect intrinsic characteristics of their haemopoietic cells, which are not environmentally determined. The further observation that endogenous colony formation represents haemopoietic stem cells in the S phase of the cell cycle at the time of X-ray exposure, has led us to propose an aetiology for NZB immunological dysfunction based on the thesis that stem cells in active cycle may constitute the physiological state during which immune potential is expressed. The expanded populations of antigen-reactive lymphocytes generated in the NZB from an augmented stem cell cycling fraction could thus account for immunological hyper-responsiveness and the simultaneous development of auto-antibodies in this strain.