Studies on anti-lymphocytic antibodies and other proteins

Abstract

The enclosed papers have been classified into five major sections whose content is as follows:

SECTION A - Describes the development of preparative ultracentrifugal and chromatographic procedures which have been used extensively in characterizing and isolating the proteins described in the subsequent sections.

SECTION B - This comprises the major part of the work and consists of a detailed investigation of the properties of heterologous antisera to mouse, rat, dog and human lymphoid tissue. These antisera have been fractionated by a variety of physico-chemical procedures including G200 sephadex gel filtration, DEAE cellulose chromatography and Porath column electrophoresis, and the major part of the antibody activity was found to be associated with the IgG fraction of most of the antisera. The whole sera and/or their IgG fractions have been shown to agglutinate, lyse and transform lymphocytes in vitro, delay the rejection of skin allografts in mice and rats and renal allografts in dogs, suppress the graft versus host reaction in mice and the onset of experimentally induced thyroiditis and autologous complex nephritis in rats. Further studies in rats have shown that anti-lymphocytic antibody also suppresses the primary humoral response to alum precipitated bovine serum albumin and sheep erythrocytes and that this effect may be antigen and strain dependent. In contrast ceil transfer and other experiments revealed that anti-lymphocytic antibody appears to have little effect on the secondary humoral response of sensitized lymphoid tissues. Finally in an attempt to elucidate the mode of action of anti-lymphocytic antibody, detailed investigations have been performed with the divalent (F(ab)₂) and univalent (Fab') fragments obtained by pepsin digestion of the intact IgG molecule, and with the non- cytotoxic derivative obtained by acid treatment. These studies revealed that the immunosuppressive properties of anti-lymphocytic IgG are dependent upon the antibody molecule possessing an intact Fc region.

SECTION C - The physico-chemical and immunological changes occurring in normal human IgG on storage have been studied and methods of isolating an abnormal 7S gamma globulin (the P M protein) and an abnormal 19S gamma globulin (rheumatoid factor) are described together with their immunological and physico-chemical properties.

SECTION D - The immunological properties of human serum oc g-niacroglobulin and a low molecular weight (S₂₀W≃3S) derivative obtained by pepsin digestion have been compared with the α₂-macroglobulin homologues of other species. The amounts of this protein in normal, pathological and cord sera have been determined immunologically and its effects upon the proteolytic and esterolytic activity of a number of enzymes have been investigated.

SECTION E - The final section details preliminary immunosuppressive studies in rodents with 'naturally' occurring and synthetically prepared polyribonuclease derivatives. Additional publications outline investigations on synovial cell proteins and on the lymphocyte transforming products of staphylococcal filtrate