Enforced bcl-xL gene expression restored splenic B lymphocyte development in BAFF-R mutant mice.
The TNFR family member BAFF-R facilitates peripheral B cell development, although it is unclear whether it promotes survival of B cells, or also initiates a differentiation program. We show that disruption of the BAFF-R encoding gene Tnfrsf13c in strain A/WySnJ mice causes a progressive decline in peripheral B cell numbers, beginning at the transitional 1 developmental stage and continuing through the mature peripheral B cell stage. Bcl-x(L) overexpression in A/WySnJ B cells decreased the turnover of transitional B cells, as determined by 5-bromo-2'-deoxyuridine labeling, and restored follicular B cell development. We conclude that the mutant A/WySnJ allele of Tnfrsf13c can be complemented through the survival signal provided by Bcl-x(L).
Amanna
Ian J
IJ
Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.
Dingwall
Jennifer P
JP
Hayes
Colleen E
CE
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D005816:Genetic Complementation Test; D005822:Genetic Vectors / Q000138:chemical synthesis; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000378:metabolism; D018626:Retroelements / Q000276:immunology; D012190:Retroviridae / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; C494812:Bcl2l1 protein, mouse; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; D018626:Retroelements; C486662:Tnfrsf13c protein, mouse; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein