Mechanisms leading to autoantibody production: link between inflammation and autoimmunity.

Hitoshi Ohmori, Naoki Kanayama

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)232-241
Number of pages10
JournalCurr Drug Targets Inflamm Allergy
Volume2
Issue number3
Publication statusPublished - Sep 2003

Fingerprint

Autoimmunity
Autoantibodies
Inflammation
B-Lymphocytes
Antibodies
Mutation
V(D)J Recombination
Immunoglobulin Class Switching
Antigens
Immunoglobulin Genes
Antibody Affinity
B-Lymphoid Precursor Cells
Germinal Center
Post Translational Protein Processing
Autoimmune Diseases
Virulence
Rheumatoid Arthritis
Clone Cells
Bone Marrow
Therapeutics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Pharmacology
  • Immunology

Cite this

Mechanisms leading to autoantibody production : link between inflammation and autoimmunity. / Ohmori, Hitoshi; Kanayama, Naoki.

In: Curr Drug Targets Inflamm Allergy, Vol. 2, No. 3, 09.2003, p. 232-241.

Research output: Contribution to journalArticle

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