Abstract
Several lines of evidence have suggested that autoreactive antibodies (Abs) may be triggered by some endogenous antigen (Ag) and undergo affinity maturation toward the target through somatic mutation coupled with isotype switching. To understand the mechanism leading to pathogenic auto-Ab production, it is of great importance to analyze endogenous Ags that can break immunologic tolerance and reveal how the triggered auto-Abs evolve to acquire pathogenicity. As for the first issue, chemically modified self-proteins that are frequently found in inflamed tissues are potential candidates. These post-translational modifications might give rise to the generation of neoepitopes to which T- and B- lymphocytes are not tolerated. In the second part, it is discussed how auto-Abs thus triggered undergo affinity maturation toward target auto-Ags. Recently, not only immature B cells in the bone marrow, but also a population of peripheral B cells have been shown to undergo secondary V(D)J recombination of immunoglobulin genes, thereby changing the Ag-specificity. This process is termed receptor revision, which, along with somatic mutation, is considered to contribute to the formation of high-affinity Abs. Receptor revision and somatic mutation may generate auto-Abs if the deletion mechanism of autoreactive clones is impaired. B cells that had undergone receptor revision have been isolated from ectopic germinal centers in inflamed tissues in patients with rheumatoid arthritis. Investigations on the link between inflammation and autoimmunity will provide new aspects for therapeutic targets in the treatment of autoimmune diseases.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.