B-cell tolerance checkpoints in health and autoimmunity

• Published in: Current opinion in immunology Vol. 20; no. 6; pp. 632 - 638
• Main Authors: Meffre, Eric, Wardemann, Hedda
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2008
• Subjects: Allergy and Immunology; Animals; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - metabolism; Autoantibodies - genetics; Autoantibodies - immunology; Autoimmunity - genetics; Autoimmunity - immunology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Gene Rearrangement, B-Lymphocyte - immunology; Humans; Immune Tolerance - immunology; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - metabolism; Receptors, Antigen, B-Cell - immunology; Receptors, Antigen, B-Cell - metabolism; Recombination, Genetic - immunology
• ISSN: 0952-7915; 1879-0372
• DOI: 10.1016/j.coi.2008.09.001

The enormous diversity of the antibody repertoire is generated by two mechanisms: recombination of immunoglobulin (Ig) gene variable (V), diversity (D), and joining (J) gene segments during the early stages of B-cell development in the bone marrow and somatic hypermutation (SHM) of functional Ig genes from antigen-activated B cells within secondary lymphoid organs. Diversity by V(D)J recombination and SHM not only provides protective humoral immunity but also generates potentially harmful clones expressing autoantibodies. Under normal circumstances, several mechanisms regulate the removal of autoreactive B cells and defects in central and peripheral B cell tolerance checkpoints are associated with the development of autoimmunity in humans.