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Cell. 1995 Jan 13;80(1):115-25.

Hypermutation generating the sheep immunoglobulin repertoire is an antigen-independent process.

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Institut National de la Santé et de la Recherche Médicale, Institut Necker, Faculté de Médecine Necker-Enfants Malades, Université Paris 5, France.


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.

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