Human B cell tolerance and its failure in rheumatoid arthritis.

Jonathan Samuels, Yen Shing Ng, Claire Coupillaud, Daniel Paget, Eric Meffre

Research output: Contribution to journalReview articlepeer-review

44 Scopus citations


Random V(D)J gene assembly generates many autoreactive B cell receptors (BCRs). In healthy donors, most autoreactive developing B cells are removed either in the bone marrow or in the periphery, revealing two B cell tolerance checkpoints. The regulation and the mechanisms that ensure this human B cell tolerance are poorly characterized, but they require proper BCR signaling. Indeed, patients with X-linked agammaglobulinemia who carry mutations in the BTK gene, which encodes an essential BCR signaling component, fail to establish proper central B cell tolerance, as demonstrated by the release of self-reactive B cells in the periphery. In autoimmune diseases such as rheumatoid arthritis (RA), B cell tolerance is broken and autoantibodies are secreted. Our recent results show that RA patients suffer from defective central and peripheral B cell tolerance checkpoints, which may favor the development of autoimmunity. Also, about half of our RA patients display unusual immunoglobulin light chain repertoires showing impaired secondary recombination regulation, which indicates that receptor editing, one of the mechanisms that normally ensures B cell tolerance, may often be defective in RA.

Original languageEnglish
Pages (from-to)116-126
Number of pages11
JournalAnnals of the New York Academy of Sciences
StatePublished - Dec 2005


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