Enhancing Antibody Induction in Mice

Rheumatoid factors (RF) have been classically defined as anti-IgG antibodies, usually of the IgM class, found in the sera of people afflicted with rheumatoid arthritis or a number of other autoimmune diseases (1-3). Antibodies with properties similar to these can be found in mice that display no pathology. We have proposed that such immune complex-specific antibodies be termed "enhancing antibodies" because of their ability to augment antibody:antigen interactions and because we believe that in most cases such antibodies arise normally, produce no concurrent pathogenesis, and may be able to aid in antigen elimination (4). In this scheme rheumatoid factors represent a subset of the enhancing antibodies produced against immune complexes. Others include those that react with new determinants or combinations of determinants generated by the close juxtaposition of antibody and antigen or conformational changes in the antigen due to bound antibody. In some mouse strains, production of auto-anti-IgG is associated with rheumatoid arthritisor lupus erythematosis-like syndromes (5, 6). In other strains RF-like material is produced in the absence of obvious disease. Strain 129/Sv mice, for example, appear to produce RF-like antibody in response to some unknown environmental stimulus in an age-dependent manner (7, 8). Mice that do not normally produce autoreactive anti-IgG in detectable amounts can be induced to do so by a number of reagents that are known to be nonspecific B cell activators, e.g. lipopolysaccharide (LPS) (9-12). In this study we have focused on enhancing antibody production and specificity in A/J mice. We show that in mice that do not spontaneously produce detectable amounts of auto-anti-IgG, very large amounts can be induced by repeated immunization with virtually any antigen and the antibody produced is of highly restricted specificity. These results confirm and extend previous work (13-15) that suggested that RF-like antibodies are produced in vivo in response to the presence of immune complexes.