Peripheral expression of RAG in human B lymphocytes in normal and pathological conditions is dependent on interleukin-6.
Establishment of the B cell repertoire is regulated by recombination activating genes RAG1 and RAG2 proteins in the bone marrow. Tolerance of autoreactivity is mainly prevented by receptor editing, i.e. synthesis of a new B cell receptor following re-expression of RAG1 and RAG2. Numerous signals can lead to RAG up-regulation, all in association with soluble cytokines. In the periphery, autoreactive B cells or low-affinity B cell receptor synthesis may appear following antigenic immune response. Receptor revision, i.e. new immunoglobulin gene rearrangement can participate to the control of these lymphocytes following new RAG1 and RAG2 re-induction. Though signals leading to this peripheral RAG up-regulation are poorly described, IL-6 seems to have a preponderant role. Therefore, the elevated levels of IL-6 secreted by activated B cells in systemic lupus erythematosus might contribute to the maintenance of abnormal RAG expression, and in turn may participate to the emergence of autoreactive B cells in the periphery.
Hillion
Sophie
S
Laboratory of Immunology Brest University Medical School, BP 824, F29609 Brest, France.
Youinou
Pierre
P
Jamin
Christophe
C
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D016654:Genes, RAG-1; D006801:Humans; D007108:Immune Tolerance; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics*; D011947:Receptors, Antigen, B-Cell
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D011947:Receptors, Antigen, B-Cell