Induction of somatic mutation in a human B cell line in vitro.
Both the B cell-surface trigger(s) and the intracellular molecular mechanism(s) of somatic hypermutation in immunoglobulin (Ig) variable region genes remain unknown, partly because of the lack of a simple and reproducible in vitro model. Here, we show that upon surface immunoglobulin cross-linking followed by co-culture with activated cloned T cells, the Burkitt's lymphoma cell line BL2 is induced to mutate its IgV(H) gene. Repeated activation of BL2 cells increased the frequency of mutation. The in vitro-induced mutations, which do not affect the IgM constant region, are point mutations distributed over the entire V(H)DJ(H) gene segment and do not show evidence of antigen-driven selection.
Denépoux
S
S
Schering-Plough Laboratory for Immunological Research, Dardilly, France.
Razanajaona
D
D
Blanchard
D
D
Meffre
G
G
Capra
J D
JD
Banchereau
J
J
Lebecque
S
S
D000595:Amino Acid Sequence; D000915:Antibody Affinity; D000941:Antigens / Q000502:physiology; D001402:B-Lymphocytes / Q000166:cytology* / Q000502:physiology; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000473:pathology; D002455:Cell Division; D002999:Clone Cells; D005803:Genes, Immunoglobulin / Q000235:genetics*; D006801:Humans; D007075:Immunoglobulin M / Q000502:physiology; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009154:Mutation; D011940:Receptor Aggregation; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology; D014407:Tumor Cells, Cultured
D000941:Antigens; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell