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Expression and Reexpression of Recombination Activating Genes: Relevance to the Development of Autoimmune States
Author(s) -
HILLION SOPHIE,
ROCHAS CAROLINE,
YOUINOU PIERRE,
JAMIN CHRISTOPHE
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1313.002
Subject(s) - germinal center , somatic hypermutation , biology , cd5 , antibody , v(d)j recombination , microbiology and biotechnology , rag2 , b cell receptor , immunology , gene , b cell , genetics , recombination
A bstract : Like all antibodies, autoreactive antibodies are generated in developing B cells in the bone marrow by variable (V), diversity (D), and joining (J) recombination under the regulation of recombination activating gene (RAG) 1 and RAG2 proteins. Deletion, anergy, and receptor edition prevent the emergence of autoreactive B cells. In the periphery, somatic hypermutation during the course of germinal center responses can lead to the emergence of autoreactive and low‐affinity antibody‐producing B cells. Deletion and receptor revision regulate autoreactive and inappropriate B cells. Defects in central or peripheral tolerance mechanisms associated with RAG expression could contribute to the appearance of autoreactive B cells. We demonstrate the presence of RAG + B cells in CD5‐expressing cells outside germinal centers. Our data suggest that receptor revision in the periphery also may occur in unusual sites when B cells are induced to express CD5. This revision may correspond to a novel regulation checkpoint in which impaired control of RAG expression could generate autoreactive B cells and lead to autoimmune states.