The signature of somatic hypermutation appears to be written into the germline IgV segment repertoire.
We present here a unifying hypothesis for the molecular mechanism of somatic hypermutation and somatic gene conversion in IgV genes involving reverse transcription using RNA templates from the V-gene loci to produce cDNA which undergoes homologous recombination with chromosomal V(D)J DNA. Experimental evidence produced over the last 20 years is essentially consistent with this hypothesis. We also review evidence suggesting that somatically generated IgV sequences from B lymphocytes have been fed back to germline DNA over evolutionary time.
Blanden
R V
RV
Division of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
Rothenfluh
H S
HS
Zylstra
P
P
Weiller
G F
GF
Steele
E J
EJ
D000818:Animals; D000916:Antibody Diversity / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D019143:Evolution, Molecular; D005785:Gene Conversion; D015321:Gene Rearrangement; D018095:Germ-Line Mutation; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation
D007135:Immunoglobulin Variable Region