title: Differentiation-associated redox-regulation in human B cell lines from stem cell/pro-B to plasma cell.
abstract: Redox-regulation of receptors and transcription factors are important for lymphocyte activation, differentiation and apoptosis. Thioredoxin (Trx) is a key redox-regulating protein and oxidative stress sensor operating in synergy with Trx-reductase and protein disulfide isomerase (PDI). The expression of Trx, PDI, and the Trx-regulated transcription-factor Pax5 were analyzed in a panel of human B cell lines and were compared with that of the Bcl-2 family proteins, also redox-controlled. The panel included representative cells from various stages: FLEB14-4 (pro-B); REH and NALM-6 (pre-B); Rael and Daudi (small mature B); U-698 and NC0467.3 (B-blasts); LP-1, U-1996, and U-266 (plasma cells). We found a significant congruence and co-variation of Trx and Bcl-2 levels in the B-lineage, with high expression levels in early stages (pro-B and pre-B) and in the late stage representing terminally-differentiated plasma cells, whereas mid-stage small resting B cells showed a very low expression. PDI increased significantly in plasma-blasts and plasma cells, indicating its importance in the highly specialized immunoglobulin assembly-machinery, including disulfide-bond isomerization. Pax5 was expressed in early and mid-stages, but was silenced in terminal stages. We conclude that the high Trx and Bcl-2-expression early and late in the B cell maturation pathway reflects a redox-strategy favoring an increased survival potential of the B cells at those stages.
authors.affiliation: Department of Biomedicine and Surgery, Division of Cell Biology, University of Linköping, SE-581 85 Linköping, Sweden.
authors.forename: Joacim
authors.initials: J
authors.lastname: Nilsson
authors.forename: Ola
authors.initials: O
authors.lastname: Söderberg
authors.forename: Kenneth
authors.initials: K
authors.lastname: Nilsson
authors.forename: Anders
authors.initials: A
authors.lastname: Rosén
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism; D010084:Oxidation-Reduction; D051757:PAX5 Transcription Factor; D010950:Plasma Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D019704:Protein Disulfide-Isomerases / Q000032:analysis / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013879:Thioredoxins / Q000032:analysis / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D013879:Thioredoxins; D019704:Protein Disulfide-Isomerases