Journal
CURRENT OPINION IN IMMUNOLOGY
Volume 20, Issue 6, Pages 632-638Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.coi.2008.09.001
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Funding
- National Institutes of Health [P01 A1061093, R01 A1071087]
- German Research Foundation [DFG WA-2590]
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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 SHIM 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.
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