The cellular basis of autoimmunity: precocious immunological maturity in NZB mice

Attempts have been made to transfer, prevent or ameliorate the autoimmune haemolytic disease that develops spontaneously in all New Zealand Black mice at 8 (4-12) months and so define the cellular basis of the automimmune process. Lymphoid cell suspensions (spleen, bone marrow, thymus) from pre-autoimmune or autoimmune NZB donors were injected intraperitoneally into intact or neonatally thymectomized syngeneic or allogeneic (BALB/c) recipients at birth or at 4 weeks. Only splenocytes from autoimmune NZB mice consistently caused anti-red cell-autoantibodies (positive Coombs reactions) to appear in pre-autoimmune NZB and also in BALB/c recipients. Moreover, the speed of the response varied and provided a measure of the recipients' ability to control the influx of the autoantibody-producing splenocytes. The immunoregulation exercised by intact NZB mice decreased, and that of their neonatally thymectomized counterparts increased between 2-3 days and one month after birth. Thus, an immunosuppressive mechanism operating via the thymus exists in NZB mice even before they are born, and the data further imply that a population of extra-thymic suppressors, presumably stemming from the bone marrow, can also be mobilized. This latter contention is supported by the finding that inocula of adult syngeneic bone marrow cells delay Coombs conversion in thymectomized NZB recipients. Preliminary experiments were also designed to resolve conflicting evidence concerning the suppressive capabilities of dissociated thymocytes of 2-week-old NZB mice.