title: Reduction in DNA binding activity of the transcription factor Pax-5a in B lymphocytes of aged mice.
abstract: Aging has been associated with intrinsic changes of the humoral immune response, which may lead to an increased occurrence of autoimmune disorders and pathogenic susceptibility. The transcription factor Pax-5 is a key regulator of B cell development. Pax-5a/B cell-specific activator protein and an alternatively spliced isoform, Pax-5d, may have opposing functions in transcriptional regulation due to the lack of a transactivation domain in Pax-5d. To study B cell-specific changes that occur during the aging process, we investigated expression patterns of Pax-5a and 5d in mature B cells of young and aged mice. RNase protection assays showed a similar transcriptional pattern for both age groups that indicates that aging has no affect on transcription initiation or alternative splicing for either isoform. In contrast, a significant reduction in the DNA binding activity of Pax-5a but not Pax-5d protein was observed in aged B cells in vitro, while Western blot analyses showed that similar levels of Pax-5a and 5d proteins were present in both age groups. The observed decrease in Pax-5a binding activity correlated with changes in expression of two Pax-5 target genes in aged B cells. Expression of the Ig J chain and the secreted form of Ig mu, which are both known to be suppressed by Pax-5a in mature B cells, were increased in B cells of aged mice. Together, our studies suggest that changes associated with the aging phenotype cause posttranslational modification(s) of Pax-5a but not Pax-5d, which may lead to an abnormal B cell phenotype in aged mice, associated with elevated levels of J chain, and secretion of IgM.
authors.affiliation: Department of Biology, The College of William and Mary, Williamsburg, VA 23187, USA.
authors.forename: J
authors.initials: J
authors.lastname: Anspach
authors.forename: G
authors.initials: G
authors.lastname: Poulsen
authors.forename: I
authors.initials: I
authors.lastname: Kaattari
authors.forename: R
authors.initials: R
authors.lastname: Pollock
authors.forename: P
authors.initials: P
authors.lastname: Zwollo
mesh_terms: D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000918:Antibody Specificity; D018941:Antigens, CD19 / Q000096:biosynthesis / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D007144:Immunoglobulin J-Chains / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051757:PAX5 Transcription Factor; D010542:Peromyscus; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D007144:Immunoglobulin J-Chains; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D020033:Protein Isoforms; D014157:Transcription Factors; D004247:DNA