THE SIGNATURE OF SOMATIC HYPERMUTATION APPEARS TO BE WRITTEN INTO THEGERMLINE IGV SEGMENT REPERTOIRE

We present here a unifying hypothesis for the molecular mechanism of s omatic hypermutation and somatic gene conversion in IgV genes involvin g reverse transcription using RNA templates from the V-gene loci to pr oduce cDNA which undergoes homologous recombination with chromosomal V (D)J DNA. Experimental evidence produced over the last 20 years is ess entially consistent with this hypothesis. We also review evidence sugg esting that somatically generated IgV sequences from B lymphocytes hav e been fed back to germline DNA over evolutionary time.