A murine model for B-cell lymphomagenesis in immunocompromised hosts: c-myc-rearranged B-cell lines with a premalignant phenotype.
Activation of c-myc or bcl-2 protooncogene is a common event in B-cell lymphomagenesis. Alone, each is insufficient to produce lymphoma, prompting the search for the additional steps required to complete the malignant phenotype. Among the existing systems of murine or human B-cell neoplasia, no commonly occurring complementary oncogenic activation has been found. This study introduces a new series of murine B-cell lines with a phenotype suggesting that such additional events might not involve intrinsic growth control, but instead host immune mechanisms which normally suppress tumorigenicity of premalignant B-cells. Four murine B-cell lines were isolated from the long-term culture of normal lymphoid tissue bearing a premalignant phenotype. (a) Their phenotype resembled naturally occurring lymphoid tumors of immunocompromised hosts with regard to c-myc activation, aberrant or absent immunoglobulin expression, preferential rearrangement of the lambda light chain locus, and a distinctive pattern of tissue invasion and tumor histology. (b) Their tumorigenicity was strictly dependent on host permissiveness correlated with immunodeficient status: C.B-17-scid greater than BALB/c-nu/nu greater than normal BALB/c much greater than other H-2d strains (NZB x NZW F1, NZB, DBA/2). (c) Host passage selected for malignant variants distinguished by a 10(4)-fold increase in tumorigenicity (as judged by limiting cell dose) and by novel tumorigenicity in nonpermissive syngeneic hosts. These features are analogous to properties of human lymphomas arising in immunocompromised states and, to our knowledge, unique among previously reported murine B-cell lines.
Department of Pathology, UCLA School of Medicine 90024.
D W
DW
Felsher
K A
KA
Denis
D
D
Weiss
D T
DT
Ando
J
J
Braun
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000473:pathology / Q000502:physiology; D002460:Cell Line / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics; D016259:Genes, myc; D007121:Immunocompetence / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009361:Neoplasm Invasiveness; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D011519:Proto-Oncogenes / Q000235:genetics
D016271:Proto-Oncogene Proteins c-myc