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Differential regulation of V(D)J recombination during development of avian B and T cells
Authors:Pickel  James M; McCormack  Wayne T; Chen  Chen-Io H; Cooper  Max D; Thompson  Craig B
Institution:1 Division of Development and Clinical Immunology, University of Alabama at Birmingham USA
3 Departments of Medicine and Microbiology and Immunology, University of Michigan, and the Howard Hughes Medical Institute USA
2 Departments of Medicine, Pediatrics, University of Alabama at Birmingham Birmingham, Alabama
4 Ann Arbor, MI, USA
Abstract:The lymphold immune system is comprised of two major cell types,B cells and T cells, originally identified in avian species.Although both lineages arise from hematopoletic stem cells,avian B cells require a period of development in the bursa ofFabricius while T cells undergo development in the thymus. Eachcell type expresses a lineage-specific antigen receptor encodedby genes created by the rearrangement of Individual membersof variable (V), diversity (D), and joining (J) gene segmentfamilies during embryonic development. In this report, we demonstratethat productive rearrangement of the TCR ß gene occursexciusively in the thymus during normal development. TCR ßrearrangements involving gene segments from the Vß1gene family can be detected beginning on day 12 of development,while rearrangements involving the other family of Vßgene segments, Vß2, were first detected on day 14of embryogenesis. In contrast, productive rearrangements ofIg light (IgL) and heavy (IgH) chain genes were not restrictedto the bursa of Fabricius. Instead, VH-DJH heavy chain rearrangementsand VL-JL light chain rearrangements were detected primarilyin the embryonic spleen, beginning as early as embryonic day10, even in birds bursectomized at 60 h of development. Withinthe spleen, Ig rearrangementwas confined to the subset of cellsthat express the chB6 surface protein. Unlike bursal lymphocytes,which express the recomblnase activating gene (RAG)-2 but notRAG-1, splenic B cell precursors also express RAG-1. The dataindicate that, while B cell precursors initiate recombinationprior to migration of the bursa of Fabricius, T cell precursorsundergo V(D)J recombination following migration to the thymus.Thus, distinct developmental mechanisms appear to regulate theprocess of receptor rearrangement during avian B and T celldevelopment.
Keywords:bursa of Fabricius  immunoglobulin  T cell receptor  thymus
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