Molecular Ig gene analysis reveals that monocytoid B cell lymphoma is a malignancy of mature B cells carrying somatically mutated V region genes and suggests that rearrangement of the kappa-deleting element (resulting in deletion of the Ig kappa enhancers) abolishes somatic hypermutation in the human.
Five cases of monocytoid B cell lymphoma (MBCL) were analyzed for somatic mutations in the rearranged V region genes. Somatic mutations were found in four of the five cases, whereas one unusual CD5+ lymphoma harbored unmutated V region genes. Since somatic mutations are introduced into V region genes of antigen-activated B cells in the course of T cell-dependent immune responses, these results suggest a derivation of the tumor B cells in MBCL from antigen-experienced mature B cells. An analysis of the kappa-deleting element in two of the cases in which mutated VH but unmutated and nonfunctional V kappa gene rearrangements were found suggests that somatic hypermutation does not take place in human rearranged V kappa region genes when the C kappa gene and the kappa enhancers have been deleted in cis by rearrangement of the kappa-deleting element.
Küppers
R
R
Institute for Genetics, University of Cologne, Germany.
Hajadi
M
M
Plank
L
L
Rajewsky
K
K
Hansmann
M L
ML
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology*; D001483:Base Sequence; D004742:Enhancer Elements, Genetic / Q000235:genetics / Q000276:immunology*; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000276:immunology*; D017384:Sequence Deletion / Q000276:immunology*
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains