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Efficient antibody diversification by gene conversion in vivo in the absence of selection for V(D)J‐encoded determinants
Author(s) -
Sayegh Camil E.,
Drury Gillian,
Ratcliffe Michael J.H.
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.22.6319
Subject(s) - biology , pseudogene , gene conversion , open reading frame , gene , immunoglobulin light chain , immunoglobulin heavy chain , immunoglobulin gene , antibody , microbiology and biotechnology , genetics , peptide sequence , recombination , genome
Antibody diversification in the bursa of Fabricius occurs by gene conversion: pseudogene‐derived sequences replace homologous sequences in rearranged immunoglobulin genes. Bursal cells expressing a truncated immunoglobulin μ heavy chain, introduced by retroviral gene transfer, bypass normal requirements for endogenous surface immunoglobulin expression. Immunoglobulin light chain rearrangements in such cells undergo gene conversion under conditions where the products are not selected based on their ability to encode a functional protein. The efficiency with which gene conversion maintains a productive reading frame exceeds 97% under such non‐selective conditions. By analysis of donor pseudogene usage we demonstrate that bursal cell development is not driven by a restricted set of antigenic specificities. We further demonstrate that gene conversion can restore a productive reading frame to out‐of‐frame VJ L junctions, providing a rationale for the elimination of cells containing non‐productive VJ L rearrangements prior to the onset of gene conversion in normal bursal cell development.