TY - JOUR
T1 - Human B cell tolerance and its failure in rheumatoid arthritis.
AU - Samuels, Jonathan
AU - Ng, Yen Shing
AU - Coupillaud, Claire
AU - Paget, Daniel
AU - Meffre, Eric
PY - 2005/12
Y1 - 2005/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33745512870&partnerID=8YFLogxK
U2 - 10.1196/annals.1358.014
DO - 10.1196/annals.1358.014
M3 - Review article
C2 - 16461794
AN - SCOPUS:33745512870
SN - 0077-8923
VL - 1062
SP - 116
EP - 126
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
ER -