Frequent occurrence of deletions and duplications during somatic hypermutation: implications for oncogene translocations and heavy chain disease.
Human naive and germinal center (GC) B cells were sorted by flow cytometry and rearranged VH region genes were amplified and sequenced from single cells. Whereas no deletions or insertions were found in naive B cells, approximately 4% of in-frame and >40% of out-of-frame rearrangements of GC B cells harbored deletions and/or insertions of variable length. The pattern of deletions/insertions and their restriction to mutated V genes strongly suggests that they result from somatic hypermutation. Deletions and insertions account for approximately 6% of somatic mutations introduced into rearranged VH region genes of GC B cells. These deletions/insertions seem to be the main cause for the generation of heavy chain disease proteins. Furthermore, it appears that several types of oncogene translocations (like c-myc translocations in Burkitt's lymphoma) occur as a byproduct of somatic hypermutation within the GC-and not during V(D)J recombination in the bone marrow as previously thought.
Goossens
T
T
Institute for Genetics, University of Cologne, 50931 Cologne, Germany. tgoossens@mac.genetik.uni-koeln.de
Klein
U
U
Küppers
R
R
D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D005434:Flow Cytometry; D017353:Gene Deletion; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006362:Heavy Chain Disease / Q000235:genetics* / Q000276:immunology; D006689:Hodgkin Disease / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region