Restricted immunoglobulin junctional diversity in neonatal B cells results from developmental selection rather than homology-based V(D)J joining.
The mechanism by which coding ends are joined during immunoglobulin (Ig) recombination is poorly understood. Recently, short sequence similarities (2-6 bp) observed at the ends of certain variable (V), diversity (D), and joining (J) gene segments of Ig have been correlated with limited junctional diversity observed in coding exons assembled from these elements. However, it is unclear whether these sequence homologies play any direct role in favoring coding joint formation by influencing the V(D)J recombination process. In this report, we demonstrate that coding sequence similarities do not influence the position of coding joints during V(D)J recombination in vivo. Instead, during embryonic development, B cells with certain joining products undergo progressive selection. Developmental selection is completed before exposure to external antigens and appears to be determined by the amino acid sequence encoded by the coding joint. We conclude that the nucleotide sequences of the coding regions do not play a major role in directing V(D)J recombination. Instead, we propose that limited Ig junctional diversity results from prenatal developmental selection of B cells based on the protein sequence of their surface Ig antigen-binding site. Sequence identities at the ends of coding segments may have evolved because they increase the likelihood that a selectable antigen-binding site is created during a random recombination process.
Pandey
A
A
Department of Internal Medicine, Howard Hughes Medical Institute, University of Michigan, Ann Arbor 48109-0650.
Tjoelker
L W
LW
Thompson
C B
CB
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000916:Antibody Diversity; D001402:B-Lymphocytes / Q000166:cytology; D001483:Base Sequence; D002060:Bursa of Fabricius / Q000196:embryology; D004372:Ducks; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D013154:Spleen / Q000166:cytology / Q000196:embryology
D009838:Oligodeoxyribonucleotides