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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2485-2492.
Prepublished online as a Blood First Edition Paper on June 20, 2006; DOI 10.1182/blood-2006-04-016063.


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TRANSPLANTATION

Host B cells produce IL-10 following TBI and attenuate acute GVHD after allogeneic bone marrow transplantation

Vanessa Rowe, Tatjana Banovic, Kelli P. MacDonald, Rachel Kuns, Alistair L. Don, Edward S. Morris, Angela C. Burman, Helen M. Bofinger, Andrew D. Clouston, and Geoffrey R. Hill

From The Queensland Institute of Medical Research; the Department of Stem Cell Transplantation, Royal Brisbane Hospital; the Department of Pathology, University of Queensland, Brisbane, Australia.

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 µMT 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 µMT 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.


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