Gene expression profiling reveals a highly specialized genetic program of plasma cells.
The formation of terminally differentiated plasma cells represents the critical final step in B-cell differentiation. In this study, utilizing oligonucleotide microarray analysis, we describe the highly specialized genetic profile exhibited by terminally differentiated plasma cells. A total of 1476 known genes were differentially expressed by plasma cells compared with B cells. Plasma cells displayed an up-regulation, induction, or a selective retention of a unique constellation of transcription factors, including members of the AP-1, nuclear factor-kappaB (NF-kappaB), nuclear factor of activated T cells (NFAT), and octamer binding factor families. Interestingly, plasma cells also displayed a down-regulation of several RNA polymerase I- related factors, consistent with terminal differentiation, and exhibited a down-regulation of the TATA box binding protein. Furthermore, plasma cells displayed alterations in multiple components of the Wnt and Notch signaling pathways and showed a unique pattern of apoptosis and proliferation-associated genes. Unexpectedly, plasma cells displayed an up-regulation of 2 factors normally associated with microenvironmental positioning of neuronal cells, reelin and neuropilin-1. These results supply insight into the developmental genetics of plasma cell differentiation and provide a foundation for further analysis of plasma cell biology.
Underhill
Gregory H
GH
Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
George
David
D
Bremer
Eric G
EG
Kansas
Geoffrey S
GS
D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000276:immunology; D018797:Cell Cycle Proteins / Q000235:genetics; D002454:Cell Differentiation; D002455:Cell Division; D003433:Crosses, Genetic; D020869:Gene Expression Profiling / Q000379:methods; D007075:Immunoglobulin M / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D000091042:Reelin Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D018797:Cell Cycle Proteins; D007075:Immunoglobulin M; D000091042:Reelin Protein; C000717128:Reln protein, mouse