The hypothesis behind this research proposal is that a kinetic analysis of the clearance of immunoglobulin sensitized, radiolabeled erythrocytes can contribute important information which will enhance our understanding of the mechanisms underlying murine immune hemolytic anemia. This approach can not only provide precise quantitative data on the clearance of sensitized erythrocytes but will also allow analysis of the various components of the process. Characterization of a specific defect(s) within this system should provide further insights into the pathogenesis of murine and human immune hemolytic anemia and the use of sensitized erythrocytes as a measure of mononuclear phagocyte system function in man. The antierythrocyte antibody response of NZB mice represents an excellent example of humoral autoimmune disease. Intraspecific hybrid clones, that we have obtained from fusion of NZB lymphocytes with a non-secreting plasmacytoma, provide homogeneous populations of monoclonal antierythrocyte antibodies possessing the specificities of their naturally occurring counterparts. Our recent demonstration that these monoclonal antibodies are capable of mediating hemolytic anemia in syngeneic BALB/c mice, in turn, provides a unique opportunity to study the in vivo effects of a specific antibody alone, without associated abnormalities of polyclonal B cell activation or altered cellular immunity. Kenetic analysis of the clearance of erythrocytes sensitized with monoclonal antibodies provides an effective tool for studying the in vivo characteristics of these antibodies as well as further defining the pathophysiology of immune mediated hemolytic disease.
| Meryhew, N L; Shaver, C; Messner, R P et al. (1991) Mononuclear phagocyte system dysfunction in murine SLE: abnormal clearance kinetics precede clinical disease. J Lab Clin Med 117:181-93 |
| Meryhew, N L; Shaver, C; Messner, R P et al. (1990) Mononuclear phagocyte system function in BALB/c mice: kinetic analysis of antibody-sensitized erythrocyte clearance in complement-depleted animals. J Lab Clin Med 115:719-28 |
