Showing papers by "Emil R. Unanue published in 1973"

Critical role of determinant presentation in the induction of specific responses in immuno-competent lymphocytes

Abstract: A detailed analysis of the role of determinant presentation in the process of triggering immunocompetent lymphocytes has been made utilizing cell-bound hapten-carrier conjugates to elicit secondary antihapten antibody responses, primarily in vitro. The results of these experiments demonstrate that: (a) hapten-protein conjugates will attach to the surface membranes of macrophages directly, in the absence of specific antibodies, in a highly immunogenic form; (b) such macrophage-bound conjugates serve as remarkedly efficient stimuli to trigger both thymus-derived (T) and bone marrow-derived (B) cells in a specific manner, lowering the optimal threshold antigen dose (in molar terms) by several logs as compared with soluble antigen; (c) the macrophage is not unique in this regard, since fibroblasts are essentially comparable in the capacity to present antigen in highly immunogenic form; (d) cell surface-bound antigen clearly favors secondary in vitro responses of the IgG as compared with the IgM antibody class; (e) in terms of triggering B or T cells, antigen bound to macrophages in the form of immune complexes does not appear to possess any appreciable advantage over equimolar quantities of directly attached antigen; (f) the increased immunogenicity of cell-bound antigen appears to reflect certain crucial, and undefined, features of cell surface membranes and not merely the stabilization of determinants on a relatively immobile surface; and (g) although the efficiency of lymphocyte triggering is markedly enhanced by cell-bound antigen, the presence of macrophages is apparently not an absolute requirement for eliciting secondary in vitro antibody responses to soluble hapten-protein conjugates. The relevance of these observations to the nature of the signal induced upon antigen interaction by specific lymphocytes and the sequential cellular events involved in the regulatory influence of activated T cells on B cell responses to antigen is discussed. We postulate that T lymphocytes are best triggered by cell-bound antigen and that after this step the activated T lymphocytes regulate the triggering of B cells with antigen.

Ligand-induced movement of lymphocyte membrane macromolecules. Iii. Relationship between the formation and fate of anti-ig-surface ig complexes and cell metabolism.

Abstract: Spleen lymphocytes were studied for the movement and interiorization of complexes of anti-Ig-surface Ig. The movement of the complex into a small, compact zone of the cell membrane (forming a cap) was inhibited by drugs that inhibited glycolysis and oxidative phosphorylation, but not by drugs that affected protein synthesis. Dead lymphocytes did not form caps. Freeze-etching techniques revealed that inhibited lymphocytes showed formation of multiple small complexes over the entire cell surface. Inhibitors of glycolysis and of oxidative phosphorylation also inhibited the interiorization and catabolism of radioiodinated anti-Ig. We hypothesize that cross-linking of all the surface Ig triggers the membrane movements that are required to pull the lattice into one zone of the cell.

Redistribution and fate of Ig complexes on surface of B lymphocytes: functional implications and mechanisms.

Abstract: This is a brief review of our recent work dealing with immunoglobulin (Ig) receptors on B lymphocytes. It emphasizes our research on the topography of surface Ig molecules and on their redistribution and fate after combination with a suitable Iigand; and discusses the possible relationship of these events with the stimulation of the lymphocyte. As a result of studies involving Ig and other surface molecules, a picture starts to develop concerning the distribution and fate of different immune complexes on eell surfaces. These results will obviously be of importance when studying complexes involving receptor Ig and various forms of antigen.