Bid is a positive regulator for donor-derived lymphoid cell regeneration in γ-irradiated recipients

• Published in: Experimental hematology 2011-09, Vol.39 (9), p.947-957.e1
• Main Authors: Shen, Hongmei, Yu, Hui, Liang, Paulina H, XuFeng, Richard, Song, Yifang, Hu, Xiaoxia, Chen, Xiaoyun, Yin, Xiao-Ming, Cheng, Tao
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; BH3 Interacting Domain Death Agonist Protein - physiology; Bone Marrow Transplantation; Flow Cytometry; Gamma Rays; Hematology, Oncology and Palliative Medicine; Lymphoid Tissue - pathology; Lymphoid Tissue - radiation effects; Mice; Mice, Transgenic; Regeneration
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2011.06.004

Objective Hematopoietic regeneration is regulated by cell survival proteins, such as the Bcl-2 family. Bid, a BH3-only protein of the Bcl-2 family, has multiple cellular functions and is involved in a variety of physiological or pathological conditions. We attempted to define its role in hematopoietic cell repopulation under the stress condition of bone marrow transplantation. Materials and Methods We performed conventional or competitive bone marrow transplantation with donor hematopoietic cells from Bid − / − or Bid+/+ mice. Flow cytometry was used for quantification of hematopoietic stem cells, hematopoietic progenitor cells, and differentiated cells in different lineages (T, B, and myeloid cells). Single cell culture and homing assays were performed to further evaluate hematopoietic stem cell functions. Hematopoietic progenitor cells were also measured by the colony-forming cell culture. Results Contrary to the widely recognized role of Bid as a pro-apoptotic protein, the absence of Bid significantly reduced the reconstitution of donor hematopoietic cells in γ-irradiated recipients. Interestingly, however, numbers of hematopoietic stem cells and hematopoietic progenitor cells and their functions were not overtly altered. Instead, the regeneration of donor T and B cells was significantly impaired in the absence of Bid. Further analysis indicated an accumulation of the triple-negative T-cell population in the thymus, and pro-B cells in the bone marrow. Conclusions Our current study demonstrates a positive impact of Bid on hematopoietic regeneration mainly due to its unique effects on donor lymphopoiesis in the transplant recipients.