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2014 ; 44
(6
): 1728-36
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TGF-?-producing regulatory B cells induce regulatory T cells and promote
transplantation tolerance
#MMPMID24700192
Lee KM
; Stott RT
; Zhao G
; SooHoo J
; Xiong W
; Lian MM
; Fitzgerald L
; Shi S
; Akrawi E
; Lei J
; Deng S
; Yeh H
; Markmann JF
; Kim JI
Eur J Immunol
2014[Jun]; 44
(6
): 1728-36
PMID24700192
show ga
Regulatory B (Breg) cells have been shown to play a critical role in immune
homeostasis and in autoimmunity models. We have recently demonstrated that
combined anti-T cell immunoglobulin domain and mucin domain-1 and anti-CD45RB
antibody treatment results in tolerance to full MHC-mismatched islet allografts
in mice by generating Breg cells that are necessary for tolerance. Breg cells are
antigen-specific and are capable of transferring tolerance to untreated,
transplanted animals. Here, we demonstrate that adoptively transferred Breg cells
require the presence of regulatory T (Treg) cells to establish tolerance, and
that adoptive transfer of Breg cells increases the number of Treg cells.
Interaction with Breg cells in vivo induces significantly more Foxp3 expression
in CD4(+) CD25(-) T cells than with naive B cells. We also show that Breg cells
express the TGF-? associated latency-associated peptide and that Breg-cell
mediated graft prolongation post-adoptive transfer is abrogated by neutralization
of TGF-? activity. Breg cells, like Treg cells, demonstrate preferential
expression of both C-C chemokine receptor 6 and CXCR3. Collectively, these
findings suggest that in this model of antibody-induced transplantation
tolerance, Breg cells promote graft survival by promoting Treg-cell development,
possibly via TGF-? production.