Hypermutation generating the sheep immunoglobulin repertoire is an antigen-independent process.
Somatic hypermutation of light chain V genes during development of B cells in sheep ileal Peyer's patches was studied in three experimental conditions: in sterile fragments of the ileum surgically isolated from the gut during fetal life, in germ-free sheep, and in animals thymectomized during early fetal life. The somatic mutation pattern was found identical to control tissues in all three experiments. The same age-dependent amount of mutations, a higher than theoretical R/S ratio in complementarity-determining regions (CDRs), and a similar clustering of mutations in CDRs were observed. The mechanism, as estimated from the silent mutation pattern, appears to target mutations to CDRs; moreover, the major V lambda genes have a specific codon usage with a high purine content at the first two bases of the codons and a low content at the third position, which, together with a specific targeting of mutations to purines, favors replacement mutations in CDRs.
Reynaud
C A
CA
Institut National de la Santé et de la Recherche Médicale, Institut Necker, Faculté de Médecine Necker-Enfants Malades, Université Paris 5, France.
Garcia
C
C
Hein
W R
WR
Weill
J C
JC
D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001482:Base Composition; D001483:Base Sequence; D003062:Codon; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D005856:Germ-Free Life; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010581:Peyer's Patches / Q000196:embryology / Q000276:immunology*; D010641:Phenotype; D012756:Sheep / Q000196:embryology / Q000235:genetics / Q000276:immunology; D013934:Thymectomy
D000941:Antigens; D003062:Codon; D007133:Immunoglobulin Joining Region; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains