Rowe Vanessa, Banovic Tatjana, MacDonald Kelli P, Kuns Rachel, Don Alistair L, Morris Edward S, Burman Angela C, Bofinger Helen M, Clouston Andrew D, Hill Geoffrey R
Bone Marrow Transplantation Laboratory, Queensland Institute of Medical Research, 300 Herston Rd, Herston, QLD 4006, Australia.
Blood. 2006 Oct 1;108(7):2485-92. doi: 10.1182/blood-2006-04-016063. Epub 2006 Jun 20.
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.
已知宿主抗原呈递细胞（APC）在异基因骨髓移植（BMT）后移植物抗宿主病（GVHD）的诱导中起关键作用，但特定APC亚群的相对贡献仍不清楚。我们通过使用B细胞缺陷型microMT小鼠作为BMT受体，在针对主要组织相容性复合体抗原的CD4依赖性GVHD模型中研究了宿主B细胞在GVHD中的作用。我们证明，相对于野生型受体，microMT受体中的急性GVHD最初会增强（死亡率：85%对44%，P < 0.01），这是BMT后早期供体T细胞增殖、扩增和炎性细胞因子产生增加的结果。在BMT时，通过提前24小时进行全身照射（TBI），受体B细胞减少了28倍，并且我们证明TBI能迅速诱导B细胞而非脾脏中的树突状细胞（DC）或其他细胞群体持续产生白细胞介素-10（IL-10）。最后，由于同源基因缺失而无法产生IL-10的受体小鼠比B细胞为野生型的受体小鼠发生更严重的急性GVHD。因此，预处理期间宿主B细胞中IL-10的诱导可减轻实验性急性GVHD。
