title: Somatic hypermutation of immunoglobulin genes is independent of the Bloom's syndrome DNA helicase.
abstract: Immunoglobulin gene somatic mutation leads to antibody affinity maturation through the introduction of multiple point mutations in the antigen binding site. No genes have as yet been identified that participate in this process. Bloom's syndrome (BS) is a chromosomal breakage disorder with a mutator phenotype. Most affected individuals exhibit an immunodeficiency of undetermined aetiology. The gene for this disorder, BLM, has recently been identified as a DNA helicase. If this gene were to play a role in immunoglobulin mutation, then people with BS may lack normally mutated antibodies. Since germ-line, non-mutated immunoglobulin genes generally produce low affinity antibodies, impaired helicase activity might be manifested as the immunodeficiency found in BS. Therefore, we asked whether BLM is specifically involved in immunoglobulin hypermutation. Sequences of immunoglobulin variable (V) regions were analysed from small unsorted blood samples obtained from BS individuals and compared with germ-line sequences. BS V regions displayed the normal distribution of mutations, indicating that the defect in BS is not related to the mechanism of somatic mutation. These data strongly argue against BLM being involved in this process. The genetic approach to identifying the genes involved in immunoglobulin mutation will require further studies of DNA repair- and immunodeficient individuals.
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, New York, NY, USA.
authors.forename: S Z
authors.initials: SZ
authors.lastname: Sack
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: German
authors.forename: N S
authors.initials: NS
authors.lastname: Green
mesh_terms: D000328:Adult; D001483:Base Sequence; D001816:Bloom Syndrome / Q000201:enzymology*; D002648:Child; D004265:DNA Helicases / Q000378:metabolism*; D004260:DNA Repair; D005803:Genes, Immunoglobulin / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D004265:DNA Helicases