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
