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Prepublished online as a Blood First Edition Paper on January 23, 2003; DOI 10.1182/blood-2002-08-2673.
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Blood, 15 May 2003, Vol. 101, No. 10, pp. 4013-4021
IMMUNOBIOLOGY
Gene expression profiling reveals a highly specialized
genetic program of plasma cells
Gregory H. Underhill,
David George,
Eric G. Bremer, and
Geoffrey S. Kansas
From the Department of Biomedical Engineering,
Northwestern University, Evanston, IL; the Pediatric Brain Tumor
Research Program, Department of Neurological Surgery, Northwestern
University Medical School and Children's Memorial Institute of
Education and Research, Chicago, IL; Robert H. Lurie Comprehensive
Cancer Center, Northwestern University Medical School, Chicago, IL; and
the Department of Microbiology-Immunology, Northwestern Medical School,
Chicago, IL.
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- B (NF-B), 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.
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