Peripheral expression of RAG in human B lymphocytes in normal and pathological conditions is dependent on interleukin-6
- PMID: 17537388
- DOI: 10.1016/j.autrev.2007.01.002
Peripheral expression of RAG in human B lymphocytes in normal and pathological conditions is dependent on interleukin-6
Abstract
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.
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