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Overexpression of Fkbp11, a feature of lupus B cells, leads to B cell tolerance
breakdown and initiates plasma cell differentiation
#MMPMID26417441
Ruer-Laventie J
; Simoni L
; Schickel JN
; Soley A
; Duval M
; Knapp AM
; Marcellin L
; Lamon D
; Korganow AS
; Martin T
; Pasquali JL
; Soulas-Sprauel P
Immun Inflamm Dis
2015[Sep]; 3
(3
): 265-79
PMID26417441
show ga
Systemic Lupus Erythematosus (SLE) is a severe systemic autoimmune disease,
characterized by multi-organ damages, triggered by an autoantibody-mediated
inflammation, and with a complex genetic influence. It is today accepted that
adult SLE arises from the building up of many subtle gene variations, each one
adding a new brick on the SLE susceptibility and contributing to a phenotypic
trait to the disease. One of the ways to find these gene variations consists in
comprehensive analysis of gene expression variation in a precise cell type, which
can constitute a good complementary strategy to genome wide association studies.
Using this strategy, and considering the central role of B cells in SLE, we
analyzed the B cell transcriptome of quiescent SLE patients, and identified an
overexpression of FKBP11, coding for a cytoplasmic putative peptidyl-prolyl
cis/trans isomerase and chaperone enzyme. To understand the consequences of
FKBP11 overexpression on B cell function and on autoimmunity's development, we
created lentiviral transgenic mice reproducing this gene expression variation. We
showed that high expression of Fkbp11 reproduces by itself two phenotypic traits
of SLE in mice: breakdown of B cell tolerance against DNA and initiation of
plasma cell differentiation by acting upstream of Pax5 master regulator gene.
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