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 i n 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...

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Bibliographic Details
Published in:Cell 1995-01, Vol.80 (1), p.115-125
Main Authors: Reynaud, Claude-Agnès, Garcia, Corinne, Hein, Wayne R, Weill, Jean-Claude
Format: Article
Language:English
Subjects:
Animals
Antigens - immunology
B-Lymphocytes - immunology
Base Composition
Base Sequence
Codon
Gene Rearrangement
Genes, Immunoglobulin
Germ-Free Life
Immunoglobulin Joining Region - genetics
Immunoglobulin lambda-Chains - genetics
Immunoglobulin Light Chains - genetics
Immunoglobulin Variable Region - genetics
Molecular Sequence Data
Mutation
Peyer's Patches - embryology
Peyer's Patches - immunology
Phenotype
Sheep - embryology
Sheep - genetics
Sheep - immunology
Thymectomy
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Summary:Somatic hypermutation of light chain V genes during development of B cells in sheep ileal Peyer's patches was studied i n 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 Vλ 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.
ISSN:0092-8674
1097-4172
DOI:10.1016/0092-8674(95)90456-5