Characterisation of a light chain loss variant of the BCL1 lymphoma.
Vaccination of BALB/c mice with idiotypic (id) IgM derived from the murine B cell lymphoma BCL1, protects the animals from challenge with tumour cells. Escape of the tumour cells from immune control is associated with the selection of variant cells which fail to express significant levels of id IgM on their cell surface. We have previously isolated one such variant, SNAG 1, and shown that, while it expresses less than 10% of the levels of surface IgM of the parental BCL1 lymphoma, it continues to synthesise id material which can be detected within the cell. In this report we present a detailed characterisation of this variant and show that the tumour cells no longer synthesise the lambda light chain. This failure to produce the light chain causes the mu heavy chains in SNAG 1 to remain marooned in the endoplasmic reticulum. The mu heavy chains in SNAG 1 have a normal mol. wt and isoelectric point, and so appear not to be mutated. This is unlike the vast majority of light chain loss variants, in which the heavy chains have been shown to contain deletions. Investigation of the mechanisms responsible for the loss of light chain synthesis demonstrated that, while mRNA for the light chain is present, and of a normal size, there was no production of light chain protein in a cell free system. This indicates that the failure to express light chain by SNAG 1 cells is due to an inability to translate the light chain mRNA into the detectable levels of lambda light chain protein.
George
A J
AJ
Lymphoma Research Unit, Tenovus Research Laboratories, Southampton General Hospital, U.K.
Foreman
R C
RC
Stevenson
F K
FK
D000818:Animals; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D015152:Blotting, Northern; D002474:Cell-Free System; D003593:Cytoplasm / Q000276:immunology; D015342:DNA Probes; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006031:Glycosylation; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000378:metabolism; D016130:Immunophenotyping; D007525:Isoelectric Focusing; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D009195:Peroxidase; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015342:DNA Probes; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D009195:Peroxidase