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• W987030207 abstract "The diversity of the preimmune antibody repertoire is generated during B-cell ontogeny by several mechanisms that depend on the assembly of complete immunoglobulin coding sequences from multiple gene segments (VDJC and VJC for the heavy and light chains respectively). Combinatorial diversity—the random joining of different V, D, and J heavy chain segments or V and J light chain segments—leads to the production of a large number of immunoglobulin heavy and light chains from a much smaller number of germline V, D, and J genes. Imprecise joining of the various gene segments, together with random association of the heavy and light chains, generate further diversity in the preimmune repertoire. Theoretically, there are about 1011 different immunoglobulin molecules that can be derived by these mechanisms from the gene segments in the murine germline. Formation of the preimmune repertoire is, however, not completely random. The repertoire is influenced by preferred V region usage, preferred VH/VL combinations, deletion of B-cells bearing highly autoreactive immunoglobulin, mechanisms to avoid autoreactivity by secondary heavy and light chain gene rearrangements, and possibly, by selection for and against particular antigenic specificities in the periphery. The study of monoclonal autoantibodies and of transgenic animals bearing autoreactive immunoglobulin genes has contributed much information about the regulation of the immunoglobulin repertoire. This review will discuss the role of VDJ and VJ immunoglobulin gene rearrangement in the generation of autoreactive specificities and the possible mechanisms of regulation of autoantibodies, with particular focus on rheumatoid factors." @default.
• W987030207 created "2016-06-24" @default.
• W987030207 creator A5072875873 @default.
• W987030207 date "1999-01-01" @default.
• W987030207 modified "2023-09-24" @default.
• W987030207 title "The Role of Variable Region Gene Rearrangements in the Generation of Autoantibodies" @default.
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• W987030207 doi "https://doi.org/10.1007/978-1-4612-1610-0_12" @default.
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