The pattern of joining (J(H)) gene usage in the human IgH chain is established predominantly at the B precursor cell stage

Preferential utilization of J(H) and D genes has been demonstrated in the rearranged IgH chain in human peripheral B cells. We report here that the same hierarchy of J(H) gene usage is observed in leukemic cells arrested in the B precursor stage of differentiation. Specifically, J(H)4 and J(H)6 accounted for 42.9% and 35.7%, respectively, of the J(H) gene usage in the leukemias compared with an expected frequency of 16.7% assuming unbiased gene usage. Within the D gene families, the DN1 gene appears to be overutilized in both populations, representing about 15% of the total gene usage compared with an expected frequency of 3.2%. Because 21 of the 36 leukemias contained only nonproductive IgH rearrangements, the preferential gene usage could not have arisen from pre-B cells that have undergone clonal selection after a productive rearrangement but before surface Ig expression. Nonproductive rearrangements exhibited the biased gene usage seen for productive rearrangements. These findings suggest that a recombination bias favoring certain segments may be the actual mechanism responsible for the apparent preferential utilization of J(H) and D genes.