CHROMOSOMAL TRANSLOCATIONS DEREGULATING C-MYC ARE ASSOCIATED WITH NORMAL IMMUNE-RESPONSES

Plasmacytomas induced in BALB/c mice by pristane consistently evidence chromosomal translocations involving the c-myc gene and one of the Ig loci. This obervation has lead to the suggestion that c-myc deregulat ion is a critical event in the generation of such tumors, However, it is not clear whether c-myc translocation is related to pristane treatm ent or occurs in normal lymphocyte populations nor whether such transl ocations occur normally, and at similar frequencies, in strains geneti cally resistant to plasmacytoma development, such as DBA/2, In order t o address these questions, a Long Distance PCR assay with single copy sensitivity was employed to assess the frequency of c-myc/IgA transloc ations in normal and immunized mice of both plasmacytoma resistant and susceptible lineages in the absence of pristane treatment. Our data d emonstrate that spontaneous translocations occur in normal DBA/2 and B ALB/c mice with no significant differences in frequency, A 3-5-fold in crease in translocation frequency was observed in mice immunized with cholera toxin, a strong stimulator of IgA responses, We conclude that c-myc deregulation by chromosomal translocation is associated with nor mal physiological processes of B-cell differentiation and, as such, ca n not be the determining factor leading to malignancy.