SOMATIC HYPERMUTATION OF IMMUNOGLOBULIN GENES IS INDEPENDENT OF THE BLOOMS-SYNDROME DNA HELICASE

Immunoglobulin gene somatic mutation leads to antibody affinity matura tion through the introduction of multiple point mutations in the antig en binding site. No genes have as yet been identified that participate in this process. Bloom's syndrome (BS) is a chromosomal breakage diso rder with a mutator phenotype. Most affected individuals exhibit an im munodeficiency 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 la ck normally mutated antibodies. Since germ-line, non-mutated immunoglo bulin genes generally produce low affinity antibodies, impaired helica se activity might be manifested as the immunodeficiency found in BS. T herefore, we asked whether BLM is specifically involved in immunoglobu lin hypermutation. Sequences of immunoglobulin variable (V) regions we re analysed from small unsorted blood samples obtained from BS individ uals 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 approac h to identifying the genes involved in immunoglobulin mutation will re quire further studies of DNA repair-and immunodeficient individuals.