bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation.
Human follicular B cell lymphomas possess a t(14;18) interchromosomal translocation that juxtaposes the putative proto-oncogene bcl-2 with the immunoglobulin (Ig) heavy chain locus. We generated minigene constructs representing the bcl-2-Ig fusion gene found at this chromosomal breakpoint. These constructs were placed into the germ line of mice to assess the effects of the t(14;18) during development. The transgene demonstrates a lymphoid pattern of expression and uniformly results in an expanded follicular center cell population. Hyperplastic splenic follicles coalesce to form massive regions of splenic white pulp. Mice over 15 weeks of age demonstrate regional lymphadenopathy with abnormal cellular infiltrates. The expanded lymphoid compartment is composed predominantly of polyclonal B220-positive, IgM/IgD-positive B cells. Provocatively, the bcl-2-Ig transgene confers a survival advantage to a population of mature B cells assessed in vitro. bcl-2-Ig transgenic mice document a prospective role for the t(14;18) in B cell growth and the pathogenesis of follicular lymphoma.
McDonnell
T J
TJ
Department of Medicine, Microbiology and Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110.
Deane
N
N
Platt
F M
FM
Nunez
G
G
Jaeger
U
U
McKearn
J P
JP
Korsmeyer
S J
SJ
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D002455:Cell Division; D002470:Cell Survival; D002874:Chromosome Mapping; D005260:Female; D005786:Gene Expression Regulation; D006942:Hypergammaglobulinemia / Q000473:pathology; D006965:Hyperplasia; D007074:Immunoglobulin G / Q000235:genetics*; D000922:Immunotoxins / Q000235:genetics*; D008221:Lymphoid Tissue / Q000378:metabolism / Q000473:pathology; D008223:Lymphoma / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D009928:Organ Specificity; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D013154:Spleen / Q000473:pathology
D007074:Immunoglobulin G; D000922:Immunotoxins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2