Host B cells produce IL-10 following TBI and attenuate acute GVHD after allogeneic bone marrow transplantation.
Host antigen-presenting cells (APCs) are known to be critical for the induction of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT), but the relative contribution of specific APC subsets remains unclear. We have studied the role of host B cells in GVHD by using B-cell-deficient microMT mice as BMT recipients in a model of CD4-dependent GVHD to major histocompatibility complex antigens. We demonstrate that acute GVHD is initially augmented in microMT recipients relative to wild-type recipients (mortality: 85% vs 44%, P < .01), and this is the result of an increase in donor T-cell proliferation, expansion, and inflammatory cytokine production early after BMT. Recipient B cells were depleted 28-fold at the time of BMT by total body irradiation (TBI) administered 24 hours earlier, and we demonstrate that TBI rapidly induces sustained interleukin-10 (IL-10) generation from B cells but not dendritic cells (DCs) or other cellular populations within the spleen. Finally, recipient mice in which B cells are unable to produce IL-10 due to homologous gene deletion develop more severe acute GVHD than recipient mice in which B cells are wild type. Thus, the induction of IL-10 in host B cells during conditioning attenuates experimental acute GVHD.
Rowe
Vanessa
V
Bone Marrow Transplantation Laboratory, Queensland Institute of Medical Research, 300 Herston Rd, Herston, QLD 4006, Australia.
Banovic
Tatjana
T
MacDonald
Kelli P
KP
Kuns
Rachel
R
Don
Alistair L
AL
Morris
Edward S
ES
Burman
Angela C
AC
Bofinger
Helen M
HM
Clouston
Andrew D
AD
Hill
Geoffrey R
GR
D000818:Animals; D000938:Antigen-Presenting Cells / Q000737:chemistry; D001402:B-Lymphocytes / Q000378:metabolism*; D016026:Bone Marrow Transplantation / Q000379:methods*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D006086:Graft vs Host Disease / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014184:Transplantation, Homologous / Q000379:methods*; D014916:Whole-Body Irradiation
D016207:Cytokines; D016753:Interleukin-10