The Induction of a Rheumatoid Factor-Like Substance in Rabbits

Abstract

Serum factors possessing some of the properties of the human rheumatoid factor(s) (RF) 1 have been produced in experimental animals. The RF and the experimentally induced factors react with various gamma globulins. The anti-gamma globulin specificities of experimentally induced serum factors can be attributed to one or more of the following mechanisms:(a) The production of antibodies against heterologous gamma globulin as in Adler's study (1) where sensitized sheep cell agglutinins developed in the serum of guinea pigs immunized with heterologous (rabbit) immune precipitates.(b) The production of iso-antibodies against rabbit gamma globulin of an allotype other than that of the host. (Studies of rabbit gamma globulin allotypes, references (9-12). This was probably operative in the studies of Milgrom and Dubiski (2, 3) who demonstrated sensitized sheep cell agglutinins in rabbits immunized with isologous antigen-antibody complexes (Escherickia coli and Proteus OX19 agglutinated by their respective rabbit antiserum). The hemagglutinating factor in each instance could be absorbed by some rabbit immune complexes but not by all.(c) Immunization against gamma globulin or gamma globulin products which were adsorbed or assimilated by bacteria, utilized for immunization, from either culture media or recent passage through animals. This was clearly

Induction of high titers of anti-IgE by immunization of inbred mice with syngeneic IgE.

“…The two pools of anti-IgE antiserum used for the gel filtration experiments described above were tested. The signals (cpm) thus obtained per 1 (24,25). It should also be of considerable interest to attempt to generate high titers of anti-IgD.…”

“…The appearance of anti-globulin autoantibodies, most frequently IgM anti-IgG, is observed after immunization with certain bacteria (1,2), heterologous proteins (3,4), or immune complexes (5,6). It has been suggested that polymers of IgG, such as occur in immune complexes, may cause the IgG to act as a thymus-independent antigen (3).…”

Low-Molecular-Weight Rheumatoid Factor*

“…This concept is supported by the findings of Milgrom and Dubiski (22) of rheumatoid factor-like substances in rabbits immunized with isologous antigen-antibody complexes. Rheumatoid factor-like substances have also been demonstrated in rabbits immunized with pure ovalbumin (23) and with E. coli grown on a synthetic medium (24). The immune complexes (ovalbumin-antiovalbumin, E. coli-anti-E. coli) produced in these animals presumably stimulated the production of rheumatoid-like factors.…”

Gamma Globulin and Antibody Formation in Vitro

“…With the sera from animals after a second injection of BGG such inactivation by mercaptoethanol treatment was not observed, indicating that most of the antibody produced was 7S rather than 19S gamma globulin (10).…”