INHERENT PROPERTIES OF SOMATIC HYPERMUTATION AS REVEALED BY HUMAN NONPRODUCTIVE V(H)6 IMMUNOGLOBULIN REARRANGEMENTS

To study inherent properties of somatic hypermutation of human immunog lobulin genes in the absence of antigen selection, mutations of human non-productive V(H)6 rearrangements enriched by subtractive hybridizat ion were characterized. Ten unique clones arising from nine nonproduct ive rearrangements were isolated. The frequency of mutation was 3.0%. Analysis of these mutations showed intrinsic bias for transitions and cytosine (C) to guanine (G) and G to C transversions. Bias for the str and of DNA targeted by mutation was not evident. Replacement mutations in the complementarity-determining region (CDR) occurred more frequen tly than expected based on the primary DNA sequence. This targeting of replacement mutations to the CDR may explain the conservation of the V(H)6 sequence in primates.