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Central and Peripheral RAG Protein Re‐expression: Underestimate Mechanisms of Tolerance?
Author(s) -
Hillion S.,
Rochas C.,
Devauchelle V.,
Youinou P.,
Jamin C.
Publication year - 2006
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2006.01801.x
Subject(s) - somatic hypermutation , biology , germinal center , peripheral tolerance , recombination activating gene , immune tolerance , immunoglobulin class switching , microbiology and biotechnology , clonal deletion , central tolerance , affinity maturation , rag2 , b cell , antibody , gene , t cell receptor , genetics , immune system , t cell , recombination
The generation of developing B cells in the bone marrow is regulated by recombination activating genes RAG1 and RAG2 proteins. They contribute to the synthesis of functional antibodies (Abs) that can present self‐reactivities following V(D)J (V, variable; D, diversity and J, joining) recombination. The emergence of autoreactive B cells is prevented by deletion through apoptosis, by stimulation blockade through anergy, or by synthesis of a new B‐cell receptor through receptor edition. In the periphery, somatic hypermutation during the course of germinal centre (GC) responses can lead to the appearance of autoreactive and low‐affinity Ab‐producing B cells. Apoptotic deletion and receptor revision regulate these autoreactive and inappropriate B cells. Moreover, the presence of RAG‐positive B cells outside GCs suggest that still uncharacterized regulation checkpoint, associated with secondary V(D)J recombination, also contribute to the regulation of autoreactivities. Failure in central and/or peripheral tolerance mechanisms associated with RAG expression could contribute to the terminal differentiation of autoreactive B cells leading to autoimmune states.