Analyses of rearranged Ig H chain V region genes of bone marrow pre-B cells demonstrate extensive sequence diversity, particularly within the third hypervariable region (HCDR3). This diversity is constrained, however, through preferential utilization of certain D gene segments and possibly VH gene segments and a preponderance of productive rearrangements, primarily those expressing D gene segments in a preferred reading frame. The predominance of productively rearranged V genes with D regions translated in a preferred frame, is, at least in part, the consequence of selective clonal expansion encompassing at least five to six divisions subsequent to VH-D-JH rearrangement. Selection for clonal expansion appears to be dependent on recognition of the nascent H chain product of certain productively rearranged genes.
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