title: Lineage and stage specificity of isotype switching in humans.
abstract: The lineage and stage specificity of human isotype switch recombination was investigated by examining the IgH gene configuration in 61 hemopoietic malignancies representing different stages of B and T cell development. An unexpectedly high frequency (20%) of IgM-producing B cell leukemias and lymphomas had undergone CH gene rearrangements and deletions consistent with attempted switch recombination. These CH gene alterations were found on productive, non-productive, and 14q+ chromosomes. These data support the concept of a non-specific (common) switch recombinase activity that is often ineffective. No evidence of such switch recombination was found in 25 mu- or mu+ pre-B cell leukemias with the single exception of a mu- pre-B leukemia in which subsets of the cells were producing gamma- or alpha-H chains. The switch recombinase activity gamma- or alpha-H chains. The switch recombinase activity may be restricted to the B cell lineage, inasmuch as CH gene deletions were not observed in T lineage malignancies.
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000276:immunology* / Q000473:pathology; D002872:Chromosome Deletion; D015322:Gene Rearrangement, B-Lymphocyte; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007134:Immunoglobulin Switch Region / Q000235:genetics* / Q000302:isolation & purification; D015448:Leukemia, B-Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014178:Translocation, Genetic
chemical_list: D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains