Induction of rheumatoid antibodies in the mouse. Regulated production of autoantibody in the secondary humoral response.

Abstract

A/J mice were found to produce autoreactive IgM anti-IgG1 in response to secondary immunization with a number of protein antigens. No anti-IgG1 was produced after a single such immunization, indicating that antigen: IgG1 antibody complexes were responsible for inducing the autoreactive response. The size of the anti-IgG1 response was in some cases massive and of the same order of magnitude as the response to the foreign immunizing material. No significant anti-IgG2a, anti-IgG2b, or anti-IgG3 response was found in mice producing anti-IgG1. Virtually all of the anti-IgG1 material produced was of the IgM class and bound to the Fc region of autologous IgG1. A component of the anti-IgG1 was shown to be able to distinguish between the two mouse IgG1 allotypes. These results suggest that self-reactive anti-IgG is a common component of the secondary immune response of mice that may have powerful physiological and immunoregulatory effects.

Efficient and selective presentation of antigen-antibody complexes by rheumatoid factor B cells.

“…The latter will thus become the selected B cell target for T cell help. This mechanism explains the negative feedback of antibody on the antibody response (10) and, in addition, the transient production of RF in the secondary immune response or upon immunization with immune complexes (11)(12)(13) .…”

Idiotypic and subgroup analysis of human monoclonal rheumatoid factors. Implications for structural and genetic basis of autoantibodies in humans.

“…The (26)(27)(28)(29)(30). These autoantibodies are produced by 3-20% of murine hybridomas derived from LPS-stimulated splenic B cells (31,32).…”

Enforced Bcl‐2 expression in B lymphocytes induces rheumatoid factor and anti‐DNA production, but the Yaa mutation promotes only anti‐DNA production

“…It has previously been shown that the IgM RF production can be induced following antigenic stimulation, likely through the activation of low-affinity RF-specific B cells by IC [3,4]. Highaffinity RF-specific B cells of the IgG isotype generated during the germinal center response are likely to be efficiently eliminated by apoptosis through interaction with excess amounts of monomeric IgG.…”

“…It has been demonstrated that IgM RF can be formed spontaneously [1] and following mitogenic or antigenic stimulation in non-autoimmune strains of mice [2][3][4]. RF formed in non-autoimmune mice are nearly always restricted to the IgM class, while lupusprone MRL-lpr/lpr mice deficient in the Fas apoptosis receptor spontaneously produce high titers of IgG RF as well as IgM RF [5][6][7].…”