Immunologic Suppression of DNA Synthesis in MOPC 104E Plasmacytoma Cells 1

Abstract

Lymphocytes respond to various mito-gens and antigens by undergoing transformation, a response characterized by increased protein and DNA synthesis followed by cell proliferation (1-3). This type of response can be either augmented or depressed by antibody (4, 5) and the ability of lymphocytes to respond to antigenic stimulation is mediated by an immunoglobulin cell surface receptor (6). For example, Op-penheim found that antigen-antibody complexes (Ab-Ag) either stimulated or suppressed lymphocyte transformation depending on whether antigen or antibody was present in excess (4). Banks (5) demonstrated that the cellular response of ovalbu-min (OA) sensitive lymphocytes was consistently depressed when OA was mixed with anti-OA antisera at concentrations equal to equivalence and two times antigen excess with one antiserum and 50 times antibody excess with another antiserum. Other concentrations varying from antigen excess to antibody excess resulted in suppression or augmentation of lymphocyte transformation, respectively. Antibody, therefore, is capable of inhibiting the immune response, either through a peripheral mechanism (action of antibody on potentially immuno-genic sites of antigen) or through a central effect (the effect of antibody on antibody-forming cells or their precursors) (7).

Anti-immunoglobulin can also regulate the immune response, as shown by Sell and Gell (8). They demonstrated that anti-immunoglobulin reagents stimulate lymphocyte transformation, and Fanger et al. (9) provided evidence that cross-linkage was required in the stimulation of transformation in rabbit peripheral lymphocytes by anti-globulin reagents. Fab and Fc fragments of goat antirabbit Ig were ineffective in the stimulation of transformation but (Fab')₂ fragments had stimulatory activity comparable to that of the intact antibody. This work supports that of Woodruff (10), who showed that univalent fragments do not cause transformation of human lymphocytes. Recently, Theis (11) demonstrated suppression of delayed hypersensitivity reactions in chickens by passive administration of anti-IgG and anti-IgM, and Her-schowitz (12) showed that anti-IgG serum suppressed the anamnestic response of rabbit lymph node cells in vitro. In these studies, anti-IgM treatment did not interfere with antibody formation.