HYPERMUTATION GENERATING THE SHEEP IMMUNOGLOBULIN REPERTOIRE IS AN ANTIGEN-INDEPENDENT PROCESS

Somatic hypermutation of light chain V genes during development of B c ells 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 thymect omized during early fetal life. The somatic mutation pattern was found identical to control tissues in all three experiments. The same age-d ependent amount of mutations, a higher than theoretical R/S ratio in c omplementarity-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; moreove r, the major V lambda genes have a specific codon usage with a high pu rine content at the first two bases of the codons and a low content at the third position, which, together with a specific targeting of muta tions to purines, favors replacement mutations in CDRs.