The impact of somatic hypermutation on the lambda light chain repertoire of individual IgM + peripheral B cells in the absence (nonproductive rearrangements) and presence (productive rearrangements) of selective influences was analyzed. In the 27 mutated nonproductive V Q J Q rearrangements obtained from individual peripheral B cells, a significantly greater mutational frequency was observed in the complementarity-determining region (CDR) in comparison to the framework region (FR), whereas the mutational frequencies in both the CDR and FR of the 100 mutated productive V Q J Q rearrangements were significantly greater. R mutations were introduced comparably in CDR and FR of nonproductive V Q J Q rearrangements, but were significantly decreased in FR of productive V Q J Q rearrangements. The majority of codons defined as hot spots for R mutations were within CDR in both the nonproductive and productive V Q J Q rearrangements. Targeting of mutations to RGYW/WRCY motifs was observed such that 38% of all mutations in the nonproductive V Q J Q rearrangements were within RGYW/WRCY motifs. Mutations in RGYW/WRCY motifs were positively selected and accounted for G 50% of all mutations in the mutated productive V Q J Q rearrangements. These data indicate that targeting of the mutational machinery and selection of mutations in these targeted motifs play major roles in influencing nucleotide changes in V Q J Q rearrangements.