![]() It has been shown that 9G4 idiotypic B cells are present and anergic in normal individuals, but actively expand into the plasma and memory cell compartments in SLE patients ( 7). In particular, a large number of the autoantibodies in SLE is of the 9G4 idiotype ( 6). One of the best known examples is systemic lupus erythematosus (SLE), where the inappropriate activation of anergic B cells and their differentiation into plasma cells that secrete autoreactive antibodies are an important contributing pathogenic mechanism. Many multifactorial autoimmune disorders involve the disruption of B cell anergy as a potential mechanism ( 5). However, anergy is not a perfect solution to control self-reactivity. Anergy is a poorly understood state whereby cells retain the ability to bind to self-antigens but are otherwise rendered insensitive to antigenic stimulation ( 4). Receptor editing entails the reactivation of recombinase activating genes (RAGs) and enables immunoglobulin genes to be rearranged to create new antigen specificities. Less self-reactive cells either undergo receptor editing or are rendered anergic ( 2, 3). Self-reactive B cells that arise due to incomplete negative selection in the bone marrow have been shown to be removed or inactivated in the periphery, with the most strongly self-reactive cells subject to clonal deletion. A tenet of modern immunology is that the adaptive immune system has evolved so as to prevent, or at least diminish responses targeting self-antigens ( 1).
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