Joseph Puri

Autoantibody‐Mediated Regulation of Tumor Growtha

CD5+ B cells in humans and Lyt-1 B cells in mice are a distinct subpopulation of B cells.I4 The CDS+B cells in healthy humans and animals secrete several types of autoantibodies. Among the autoantigens recognized by the antibody products of CD5+B cells are the Fc portion of IgG, single-stranded (ss) DNA, cryptic haptens on erythrocytes, membrane constituents of nucleated cells including lymphocytes, and several internal cellular proteins.”I4 In this paper we refer to these antibodies as naturally occurring autoantibodies (NOA), denoting the fact that these antibodies are present in healthy humans or animals that were not intentionally immunized. The physiologic function of NOA, if any, is unknown. Grabar was the first to postulate that such antibodies fulfill a “household” function by opsonizing senescent cells, thus enabling their rapid clearance from the system.I5 Other researchers postulate a “first-line defense” function similar to that of cellular components of natural immunity.16 One of the most striking characteristics of many NOA is their polyreactivity, that is, their ability to interact with more than one antigen.7*’2J7-’9 Thus NOA, although recognizing and interacting with autoantigens, may also interact with nonself antigens such as bacterial components. As suggested by Notkins,’ the polyreactivity of NOA could be attributed to one or more of the following mechanisms: (a) recognition of a particular epitope expressed on proteins from different sources or on different cells; (b) a chemical similarity between the epitope on a certain protein and another epitope on

Inhibition of release of arachidonic acid, superoxide, and IL-1 from human monocytes by monoclonal anti-HLA class II antibodies: Effects at proximal and distal points of inositol phospholipid hydrolysis pathway

Incubation of human elutriator-purified monocytes with anti-HLA-DR or DQ antibody inhibited the release of arachidonic acid induced by serum-treated zymosan (STZ), a phagocytic stimulus that is known to induce inositol phospholipid hydrolysis and Ca2+ influx. However, only anti-HLA-DR antibody partially inhibited STZ-induced inositol phospholipid hydrolysis and concanavalin-A-induced Ca2+ influx. Incubation with anti-HLA-DR or -DQ antibody inhibited phorbol ester-induced AA release as well as superoxide production and IL-1 release. Inhibition of monocyte function by anti-class II antibodies was not accompanied by cAMP elevation. Furthermore, addition of exogenous db-cAMP and other agents (forskolin, cholera toxin, or 3-isobutyl-1-methyl-xanthine) that increase cAMP levels through different mechanisms, a one or in combination with anti-HLA antibodies, had no inhibitory effect on factor release. Our results demonstrate that perturbation of class II molecules down-modulates cell activation at more than one point of the signal transduction pathway with dominant inhibition distal to inositol phospholipid hydrolysis. They also suggest that the inhibition by anti-HLA class II antibody is probably not mediated via cAMP elevation.

Regulation of Antigen Binding to T Cells: The Role of Products of Adherent Cells, and the H-2 Restriction of the Antigen Bound

We have described recently that antigen binding to T cells is influenced by a soluble factor of peritoneal adherent cells (MF). It was observed by microscopic autoradiography of radio-labeled antigen bound to nylon wool effluent T cells, that the number of antigen binding T cells increases several fold as a result of incubation with MF for 2 hr before antigen binding. We have shown that this effect is antigen specific and that the target cell of MF action is an Lyt-1+, 2−, 3− cell. It was also observed that H-2 identity is not required between the antigen binding T cells and the adherent cells from which the MF was produced. In contrast the Ir type of the antigen binding T cell enriched population did determine whether increased antigen binding could be observed (5). In a subsequent study we have attempted to define the most important molecules involved in antigen binding to T cells. Alloantisera specific to distinct components controlled by the H-2 complex and purified antibodies against immunoglobulin V regions were used to inhibit antigen binding to T cells. It was found that antigen binding to Lyt-1+, MF sensitive non immune T cells is inhibited by anti Ia, anti idiotype (C3H,SW anti-(T,G)-A--L) and anti-VH antibodies. No inhibition was observed when these cells were treated with anti-H-2K, anti-H-2D and anti-Vγ antibodies (3).