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Reduction in DNA binding activity of the transcription factor Pax-5a in B lymphocytes of aged mice

Anspach, J
; 
Poulsen, G
; 
Kaattari, I
; 
Pollock, R
; 
Zwollo, P
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-Sd, may have opposing functions in transcriptional regulation due to the lack of a transactivation domain in Pax-Sd. To study B cell-specific changes that occur during the aging process, we investigated expression patterns of Pax-Sa and Sd 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-Sa but not Pax-Sd protein was observed in aged B cells in vitro, while Western blot analyses showed that similar levels of Pax-Sa and Sd proteins were present in both age groups. The observed decrease in Pax-Sa 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-Sa 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-Sa but not Pax-Sd, which may lead to an abnormal B cell phenotype in aged mice, associated with elevated levels of J chain, and secretion of IgM.
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2001-01-01
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Aquatic Health Sciences Peer-Reviewed Articles, Cell Differentiation; Factor Bsap; Activator Protein; Chain Gene; 3'Alpha Enhancer; Nf-Hb
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Virginia Institute of Marine Science
DOI
https://doi.org/10.4049/jimmunol.166.4.2617
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https://scholarworks.wm.edu/handle/internal/17391
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