CHARACTERISTICS OF A SPONTANEOUS MONOCLONAL THYMOCYTOTOXIC ANTIBODY FROM NEW-ZEALAND BLACK MICE - RECOGNITION OF A SPECIFIC NTA DETERMINANT

Naturally occurring thymocytotoxic autoantibodies (NTA) were described both in humans and in mice with systemic lupus erythematosis (SLE), and have been reported to be preferentially reactive with T suppressor as compared to T helper cells. Although NTA has been shown by some groups of investigators to induce autoantibodies in normal strains of mice, other researchers have suggested that NTA has only a minor, if any, role in murine lupus. The characteristics of a monoclonal antibody (TC-17) derived from the fusion of 4-mo.-old NZB spleen cells with P3-X63-AG8, 653 plasmacytoma cells were studied. This monoclonal IgM reagent is cytotoxic for .apprx. 40% of total thymocytes, 50% of cortical thymocytes, < 1% of cortisol-resistant thymocytes, 10% of splenocytes and lymph node cells and < 3% of bone marrow and fetal liver cells. The thymocytotoxicity can be absorbed by thymocytes but not by brain cells. Although NZB, NZW, NFS and BALB/c thymocytes all manifest reactivity with TC-17, there was considerable difference between strains with respect to antigen density; NZB thymocytes have the highest density. By fluorescence-activated cell sorter analysis, TC-17 occurs independently of Lyt-1, Lyt-2 and T helper cell-specific antigens, and is more prevalent on larger proliferating thymocytes. TC-17 augments the response to sheep red blood cells but does not influence responses to TI-1 (trinitrophenyl-bovine albumin) or TI-2 (dinitrophenyl-Ficoll) antigen and production of lipopolysaccharide-induced B cell colonies. Evidently, TC-17 recognizes a new T cell antigen, probably one involved in T cell differentiation. Because this monoclonal NTA reacts with only 40% of thymocytes, and is not absorbed with brain, it would not have been detected in mouse sera by using previously published methods. NTA are a heterogeneous group of autoantibodies; some specificities such as TC-17 went unrecognized in the past, and may be important either for disease pathogenesis or for secondary immunologic abnormalities.