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2017 ; 12
(6
): e0179793
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Characterization of human FCRL4-positive B cells
#MMPMID28636654
Jourdan M
; Robert N
; Cren M
; Thibaut C
; Duperray C
; Kassambara A
; Cogné M
; Tarte K
; Klein B
; Moreaux J
PLoS One
2017[]; 12
(6
): e0179793
PMID28636654
show ga
FCRL4 is an immunoregulatory receptor that belongs to the Fc receptor-like (FCRL)
family. In healthy individuals, FCRL4 is specifically expressed by memory B cells
(MBCs) localized in sub-epithelial regions of lymphoid tissues. Expansion of
FCRL4+ B cells has been observed in blood and other tissues in various infectious
and autoimmune disorders. Currently, the mechanisms involved in pathological
FCRL4+ B cell generation are actively studied, but they remain elusive. As in
vivo FCRL4+ cells are difficult to access and to isolate, here we developed a
culture system to generate in vitro FCRL4+ B cells from purified MBCs upon
stimulation with soluble CD40 ligand and/or CpG DNA to mimic T-cell dependent
and/or T-cell independent activation, respectively. After 4 days of stimulation,
FCRL4+ B cells represented 17% of all generated cells. Transcriptomic and
phenotypic analyses of in vitro generated FCRL4+ cells demonstrated that they
were closely related to FCRL4+ tonsillar MBCs. They strongly expressed inhibitory
receptor genes, as observed in exhausted FCRL4+ MBCs from blood samples of
HIV-infected individuals with high viremia. In agreement, cell cycle genes were
significantly downregulated and the number of cell divisions was two-fold lower
in in vitro generated FCRL4+ than FCRL4- cells. Finally, due to their reduced
proliferation and differentiation potential, FCRL4+ cells were less prone to
differentiate into plasma cells, differently from FCRL4- cells. Our in vitro
model could be of major interest for studying the biology of normal and
pathological FCRL4+ cells.