Expression of the BLM gene in human haematopoietic cells

Bloom's syndrome (BS) is a rare autosomal recessive disorder characterized by stunted growth, sun-sensitive erythema and immunodeficiency. Chromosomal abnormalities are often observed. Patients with BS are highly predisposed to cancers. The causative gene for BS has been identified as BLM. The forme r encodes a protein, which is a homologue of the RecQ DNA helicase family, a family which includes helicases such as Esherichia coli RecQ, yeast Sgs1, and human WRN. WRN is encoded by the gene that when mutated causes Werner' s syndrome. The function of BLM in DNA replication and repair has not yet b een determined, however. To understand the function of BLM in haematopoieti c cells and the cause of immunodeficiency in BS, expression of the BLM gene in various human tissues and haematopoietic cell lines was analysed and th e involvement of BLM in immunoglobulin rearrangement examined. In contrast to WRN, BLM was expressed strongly in the testis and thymus. B, T, myelomon ocytic and megakaryocytic cell lines also expressed BLM. All of the examine d sequences at the junction of the variable (V), diversity (D) and joining (J) regions of the immunoglobulin heavy-chain genes were in-frame, and N-re gion insertions were also present. The frequency of abnormal rearrangements of the T cell receptor was slightly elevated in the peripheral T cells of patients with BS compared with healthy individuals, whereas a higher freque ncy of abnormal rearrangements was observed in the cells of patients with a taxia-telangiectasia (A-T). In DND39 cell lines, the induction of sterile t ranscription, which is required for class switching of immunoglobulin heavy -chain constant genes, was correlated with the induction of the BLM gene. T aking into consideration all these results, BLM may not be directly involve d in VDJ recombination, but is apparently involved in the maintenance of th e stability of DNA.