Antibody Mediated Effector Cell Immunoregulation

Woodland, Robert

Abstract

We have shown that antibody to antigen can specifically inhibit both antibody secretion by B effector cells and the cytotoxicity mediated by T effector cells. Antibody acts through the cell-associated immunogen which has been repeatedly demonstrated on these cells. We have proposed that this represents a form of immunoregulation that provides an important homeostatic control mechanism for the reversible inhibition of committed effector lymphocytes. To date our research has focused on antibody responses induced with thymus-independent antigens. To determine the true scope of this regulatory system we will examine the inhibition of effector B cells induced with thymus dependent antigens using antibodies for haptenic, native, or denatured carrier determinants. Using a panel of antibody-secreting hybridomas, or PFC induced in vivo or in vitro with TI antigens we will determine, by physiochemical techniques, the molecular associations between cell-surface antigen, immunoglobulin (Ig) and/or products of the major histocompatibility complex. We will also determine the mechanism by which the inhibitory signal is delivered using inhibitors known to interfere with ligand induced B cell activation. We will analyze autoimmune NZB mice, which show a hyposensitivity to downregulation and aged mice, which show a hypersensitivity to downregulation, for their responses to antigen, or Ig specific antibody mediated immunoregulation. Lastly, we would like to determine the mechanism by which hapten specific cytotoxic T effector cells are inhibited by anti-hapten antibody. We have chosen to examine this immunoregulatory pathway because it provides a new and conceptually important homeostatic control mechanism on the function of committed effector cells, as well as a new model system to study the rapid and reversible regulation of cell function by transmembrane signaling events.