Alternative rearrangements of immunoglobulin light chain genes in human leukemia

Immunoglobulin heavy and light chain genes undergo rearrangement before they can be expressed by B-cells. A sequence of successive rearrangements has been proposed, suggesting that these events are initiated on heavy chain genes and are followed by sequential attempts of light chain gene rearrangements involving kappa gene alleles before lambda genes. This hypothesis, mainly established on B-cell clones of medullary origin, is consistent with the predominance of kappa chains among human serum immunoglobulins. However, data from tumors or normal lymphoid tissue suggest that lambda chain expression could be favored outside the bone marrow, due to an alternative rearrangement hierarchy. We investigated this hypothesis further on 17 leukemia samples. In three instances, we observed that lambda genes had undergone rearrangement while kappa genes remained in germline configuration. These data support the hypothesis of occasional alternative rearrangements of light chain genes.