TRANSPLANTATION OF AUTO-IMMUNE POTENTIAL .3. IMMUNOLOGICAL HYPER-RESPONSIVENESS AND ELEVATED ENDOGENOUS SPLEEN COLONY FORMATION IN LETHALLY IRRADIATED RECIPIENTS OF NZB BONE-MARROW CELLS

Abstract

Previous studies demonstrated that NZB .fwdarw. 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 to sheep erythrocyte immunization and to in vitro spleen cell stimulation by T[thymus-derived]-cell mitogens. The hyperproliferative properties of the stem cells and immunocytes of the NZB reflect intrinsic characteristics of their hemopoietic cells, which are not environmentally determined. The observation that endogenous colony formation represents hemopoietic stem cells in the S phase of the cell cycle at the time of X-ray exposure has led to the proposal of an etiology for NZB immunological dysfunction. This proposal is 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 autoantibodies in this strain.