Immunoglobulin V gene utilization in chronic lymphocytic leukemia and non-Hodgkin's B cell lymphomas.
Chronic lymphocytic leukemia (CLL) represents a malignancy of the CD5 B cell. Such CD5 B cells constitute a minor B cell subpopulation in normal adults that recently has been implicated as a source of IgM autoantibodies. NHL of follicular center cell origin, on the other hand, generally do not co-express CD5, and may be considered neoplasms of B cells from a lineage(s) or differentiation stage(s) distinct from that of the CD5 B cell. We examined antibody-expressing malignant B cells from patients with CLL for reactivity with each of several mouse monoclonal antibodies (mAb) specific for immunoglobulin (Ig) cross-reactive idiotypes (CRI) associated with human autoantibodies. Nearly 20% of all Ig-expressing CLL were recognized by a mAb specific for a rheumatoid factor (RF) heavy-chain associated CRI. Furthermore, approximately 20% of the kappa light chain expressing CLL reacted with 17.109, a mAb specific for a kappa-light-chain-associated CRI. In contrast, NHL that do not co-express the CD5 surface antigen apparently react with these anti-CRI mAbs at significantly lower frequencies. None of the forty CD5-negative NHL tested reacted with the mAb specific for the Ig heavy chain associated CRI. Moreover, only one of 30 kappa light chain expressing CD5-negative NHL tested reacted with 17.109. We examined the molecular basis for the high frequency expression of autoantibody-associated CRIs in CLL. Analyses of the Ig kappa light chain cDNA reveals remarkable conservation in the nucleic acid sequence of the kappa light chain variable region gene (Vk gene) expressed by 17.109-reactive leukemic cells from unrelated patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Kipps
T J
TJ
Department of Basic and Clinical Research, Scripps Clinic, La Jolla, CA 92037.
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000378:metabolism*; D005803:Genes, Immunoglobulin; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D008969:Molecular Sequence Data