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• W33130187 abstract "Naturally occurring autoantibodies (NAbs) are typically polyreactive, bind with low affinity to a discrete set of autoantigens and are encoded by variable region genes in germline configuration. They differ from disease-associated autoantibodies (autoAb), which are mostly monoreactive, somatically mutated and of high affinities. Structure-function studies have shown that polyreactivity of NAbs relies on the somatically generated complementarity determining region, CDR3, of the heavy chain. This finding suggested that NAb-producing B cells were positively selected from the pre-immune B-cell repertoire. The biological significance of this selection remains, however, unclear. Data originating mainly from transgenic mice have shown that mature NAb-producing B cells are frequently ignorant toward their antigen, possibly due to their low affinity, though active tolerance mechanisms are not excluded. An important issue is whether NAb-producing B cells constitute the pool from which pathologic auto Ab emerge after autoantigen-driven maturation. We summarize results obtained in mouse models, showing that some infectious agents are able to induce an autoantigen-driven activation of certain NAb-producing B cells. However direct proof that selection by autoantigen may lead to somatic hypermutation are still lacking. Other data tend to suggest that pathologic auto Abs may derive from non-autoimmune B cells that have diversified by somatic hypermutation of their variable region genes." @default.
• W33130187 created "2016-06-24" @default.
• W33130187 creator A5011115621 @default.
• W33130187 creator A5067779835 @default.
• W33130187 date "2012-01-01" @default.
• W33130187 modified "2023-10-17" @default.
• W33130187 title "Control of B Cells Expressing Naturally Occurring Autoantibodies" @default.
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• W33130187 doi "https://doi.org/10.1007/978-1-4614-3461-0_11" @default.
• W33130187 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22903672" @default.
• W33130187 hasPublicationYear "2012" @default.
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