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2017 ; 16
(11
): 1104-1117
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Hypoxia favors the generation of human plasma cells
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Schoenhals M
; Jourdan M
; Bruyer A
; Kassambara A
; Klein B
; Moreaux J
Cell Cycle
2017[Jun]; 16
(11
): 1104-1117
PMID28463531
show ga
Plasma cells (PCs) generation occurs in hypoxic conditions in vivo, whereas the
relevance of O(2) pressure in PC differentiation remains unknown. Using our in
vitro PC differentiation model, we investigated the role of hypoxia in PC
generation. Hypoxia increases the generation of plasmablasts (PBs) starting from
memory B cells, by increasing cell cycle and division number. Reactome analysis
demonstrated a significant enrichment of genes involved in HIF1? and HIF2?
transcription factor network, metabolism and MYC related pathways in hypoxic
compared with normoxic PBs. Hypoxia-induced metabolism alteration and MYC pathway
are involved in malignant PC pathophysiology. Therefore, the expression of 28 out
of the 74 genes overexpressed in hypoxic PBs compared with normoxic ones was
found to be associated with an adverse prognosis (event free survival and overall
survival) in newly diagnosed multiple myeloma patients. According to the role of
hypoxia in supporting PBs generation through cell cycle induction, c-MYC
activation and metabolism alteration, it could be involved in plasma cell
tumorigenesis.
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