Skewed B cell VH family repertoire in Bcl-2-Ig transgenic mice.
The proto-oncogene Bcl-2 is normally expressed in B lineage cells in a stage specific manner and extends cell survival. Deregulated Bcl-2 expression has been shown to cause a major expansion in surface IgM and IgD positive B cells. In this report, the influence of deregulated expression of Bcl-2 on the VH repertoire of B cells was studied. This was accomplished by stimulating B cells from both adult and fetal Bcl-2-Ig transgenic mice and their normal littermates using the polyclonal activator lipopolysaccharide. Activated cells were then analyzed by in situ hybridization using radiolabeled C mu and VH gene probes. The D-proximal VH families 7183 and Q52 were preferentially expressed in the adult transgenic mice compared to their normal littermates. VH 7183 and Q52 were also over-represented in fetal transgenic mice but not to a greater extent than that observed with normal fetuses. These results demonstrate that the overproduction of Bcl-2, which prolongs cell survival independent of affecting proliferation, substantially alters the VH gene repertoire.
Yeh
T M
TM
Department of Microbiology, University of Texas Health Science Center, San Antonio 78284-7758.
Korsmeyer
S J
SJ
Teale
J M
JM
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D005803:Genes, Immunoglobulin; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic / Q000196:embryology / Q000235:genetics / Q000276:immunology*; D010950:Plasma Cells / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D013154:Spleen / Q000166:cytology / Q000196:embryology
D007135:Immunoglobulin Variable Region; D008070:Lipopolysaccharides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2