title: Decreased immunoglobulin deposition in tumors and increased immature B cells in p53-null mice.
abstract: Recent studies have hinted that there may be a relationship between p53 and the immune response. In preliminary experiments, we found significantly decreased levels of immunoglobulin deposition in 13 of 16 p53-null tumors compared with 2 of 17 tumors derived from p53 +/- mice. We further explored the effect of p53 on B-cell development and function. p53-null mice contained more splenic white pulp and more immature B cells in the bone marrow compared with p53 +/- mice. p53-null B cells were hyperresponsive to proliferative challenge but were not more resistant to signal-induced apoptosis. Several p53 DNA-binding sites were localized to the regulatory regions of immunoglobulin heavy and light chain genes, including the KII site, which serves as an enhancer for rearrangement of the mouse kappa chain J cluster genes. Levels of p53 protein and the kappa chain sterile transcript increased after exposure of pre-B cells to the DNA damaging agents etoposide and Adriamycin. Our observations suggest that p53 may be involved in B-cell maturation and may relay certain stress signals to affect B-cell function.
authors.affiliation: Laboratory of Molecular Oncology and Cell Cycle Regulation, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
authors.forename: L
authors.initials: L
authors.lastname: Shick
authors.forename: J H
authors.initials: JH
authors.lastname: Carman
authors.forename: J K
authors.initials: JK
authors.lastname: Choi
authors.forename: K
authors.initials: K
authors.lastname: Somasundaram
authors.forename: M
authors.initials: M
authors.lastname: Burrell
authors.forename: D E
authors.initials: DE
authors.lastname: Hill
authors.forename: Y X
authors.initials: YX
authors.lastname: Zeng
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: K G
authors.initials: KG
authors.lastname: Wiman
authors.forename: K
authors.initials: K
authors.lastname: Salhany
authors.forename: T R
authors.initials: TR
authors.lastname: Kadesch
authors.forename: J G
authors.initials: JG
authors.lastname: Monroe
authors.forename: L A
authors.initials: LA
authors.lastname: Donehower
authors.forename: W S
authors.initials: WS
authors.lastname: el-Deiry
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001665:Binding Sites; D015153:Blotting, Western; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005809:Genes, Regulator; D016158:Genes, p53 / Q000235:genetics* / Q000276:immunology*; D005838:Genotype; D005909:Glioblastoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007136:Immunoglobulins / Q000235:genetics* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D018655:Lymphocyte Count; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D008070:Lipopolysaccharides