Immunoglobulin G amplifies the production of regulatory rheumatoid factor in vitro through idiotype-anti-idiotype interactions

ABSTRACT

Immunoglobulin G can inhibit antibody response. The mechanism of immunosuppression by immunoglobulins remains unknown. Recently, we found a new factor of immunoregulation referred to as regulatory rheumatoid factor (regRF). RegRF prevents autoimmunity and reduces experimental autoimmune reactions. RegRF comprises a population of anti-idiotypic antibodies that have a unique paratope specific to the antigen-binding sites of the antibodies, and a shared paratope specific to neoepitopes of IgG Fc fragments. Given the specificity of regRF, we can anticipate that IgG would be able to induce regRF production, and consequently that the immunosuppressive effect of IgG may be mediated by regRF. We found that IgG induces regRF production in a culture of B lymphocytes obtained from the red bone marrow of intact rats. IgG does not expose neoepitopes recognized by the shared paratope of regRF, and does not acquire them in culture. Therefore, the stimulation of regRF production induced by IgG is not a result of the interaction between the shared paratope of regRF and the neoepitopes of IgG. Fc fragments of IgG are unable to stimulate regRF production. Fab fragments inhibit spontaneous regRF production. F(ab´)₂ fragments stimulate regRF production in lymphocyte culture. We theorize that IgG activates regRF-producing lymphocytes through idiotype-anti-idiotype interactions.

KEYWORDS:

• Rat immunoglobulin G
• regulatory rheumatoid factor
• red bone marrow lymphocytes
• immunoglobulin G fragments

Acknowledgments

We are grateful to Jennifer Guernsey for editorial assistance.

Conflicts of interest

The authors report no conflicts of interest.

Additional information

Funding

This work was supported by Russian Foundation for Basic Research [grant numbers 18-315-00424] and the scholarship of the President of the Russian Federation to young scientists and post-graduate students [No. SP-1630.2018.4].