Differential regulation of V(D)J recombination during development of avian B and T cells.
The lymphoid immune system is comprised of two major cell types, B cells and T cells, originally identified in avian species. Although both lineages arise from hematopoietic stem cells, avian B cells require a period of development in the bursa of Fabricius while T cells undergo development in the thymus. Each cell type expresses a lineage-specific antigen receptor encoded by genes created by the rearrangement of individual members of variable (V), diversity (D), and joining (J) gene segment families during embryonic development. In this report, we demonstrate that productive rearrangement of the TCR beta gene occurs exclusively in the thymus during normal development. TCR beta rearrangements involving gene segments from the V beta 1 gene family can be detected beginning on day 12 of development, while rearrangements involving the other family of V beta gene segments, V beta 2, were first detected on day 14 of embryogenesis. In contrast, productive rearrangements of Ig light (IgL) and heavy (IgH) chain genes were not restricted to the bursa of Fabricius. Instead, VH-DJH heavy chain rearrangements and VL-JL light chain rearrangements were detected primarily in the embryonic spleen, beginning as early as embryonic day 10, even in birds bursectomized at 60 h of development. Within the spleen, Ig rearrangement was confined to the subset of cells that express the chB6 surface protein. Unlike bursal lymphocytes, which express the recombinase activating gene (RAG)-2 but not RAG-1, splenic B cell precursors also express RAG-1. The data indicate that, while B cell precursors initiate recombination prior to migration of the bursa of Fabricius, T cell precursors undergo V(D)J recombination following migration to the thymus. Thus, distinct developmental mechanisms appear to regulate the process of receptor rearrangement during avian B and T cell development.
Division of Development and Clinical Immunology, University of Alabama at Birmingham.
J M
JM
Pickel
W T
WT
McCormack
C H
CH
Chen
M D
MD
Cooper
C B
CB
Thompson
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002642:Chick Embryo; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D018398:Homeodomain Proteins; D007133:Immunoglobulin Joining Region / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000276:immunology*
D018398:Homeodomain Proteins; D007133:Immunoglobulin Joining Region; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D011506:Proteins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; C064658:RAG-1 protein