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.