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

Royal Brisbane Hospital, Brisbane, Queensland, Australia
Blood (Impact Factor: 10.45). 11/2006; 108(7):2485-92. DOI: 10.1182/blood-2006-04-016063
Source: PubMed


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.

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    • "As previously stated B cells are also able to function as APCs and given the regulatory action of B10 cells in autoimmunity and cancer, their involvement in graft versus host disease has been hypothesized and explored. Rowe and colleagues demonstrated that B cell-deficient μMT mice receiving BM transplantation demonstrated higher mortality rates due to acute GVHD than wild type recipients (76). This seems to be directly linked to the ability of B cells acting as APCs in reducing the proliferation of CD4+ T cells as well as the production of pro-inflammatory cytokines within the donor. "
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    • "Many studies have suggested a regulatory role for B lymphocytes in immune responses involved after HSCT. Rowe et al (2006) have shown in a murine model that interleukin (IL)-10 secretion by host B lymphocytes could decrease acute GvHD incidence after HSC allograft. B cell-deficient mice more frequently developed more severe acute GvHD. "
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