Bone Marrow Transplantation Results in Human Donor Blood Cells Acquiring and Displaying Mouse Recipient Class I MHC and CD45 Antigens on Their Surface

Abstract

BackgroundMouse models of human disease are invaluable for determining the differentiation ability and functional capacity of stem cells. The best example is bone marrow transplants for studies of hematopoietic stem cells. For organ studies, the interpretation of the data can be difficult as transdifferentiation, cell fusion or surface antigen transfer (trogocytosis) can be misinterpreted as differentiation. These events have not been investigated in hematopoietic stem cell transplant models.Methodology/Principal FindingsIn this study we investigated fusion and trogocytosis involving blood cells during bone marrow transplantation using a xenograft model. We report that using a standard SCID repopulating assay almost 100% of the human donor cells appear as hybrid blood cells containing both mouse and human surface antigens.Conclusion/SignificanceHybrid cells are not the result of cell-cell fusion events but appear to be due to efficient surface antigen transfer, a process referred to as trogocytosis. Antigen transfer appears to be non-random and includes all donor cells regardless of sub-type. We also demonstrate that irradiation preconditioning enhances the frequency of hybrid cells and that trogocytosis is evident in non-blood cells in chimera mice.

Immunomodulatory Effects of Different Cellular Therapies of Bone Marrow Origin on Chimerism Induction and Maintenance Across MHC Barriers in a Face Allotransplantation Model

“…(2016) 64:299-310 307 (Nygren et al 2004), kidney (Bonde et al 2010 and VCA (Ajiki et al 2005) transplantation. The survival and impact of DRCC is unknown (Kashofer et al 2006) and these cells may simply result either from in vivo cell fusion or from the transfer of plasma membrane fragments (trogocytosis) (Yamanaka et al 2009). Trogocytosis is the mechanism when large amounts of surface proteins can be transferred between the cells.…”

Intra-hematopoietic cell fusion as a source of somatic variation in the hematopoietic system

“…1C,D), distinguishing cells co-expressing donor-host markers from doublets. To exclude ambiguity from surface antigen or membrane transfer between donor and host hematopoietic cells (Yamanaka et al, 2009) Fig. S1).…”

“…S2). This is probably due to cell membrane sharing (trogocytosis) between cells (Yamanaka et al, 2009). As evident from the decreased frequency of fusion events subsequently validated by genetic assays, FACS is suitable for the prospective recovery, but suffers from lower specificity.…”

“…Co-expression of both CD45 donor and host isotype cell surface markers after ablative transplantation is widely attributed to experimental artifact, or considered evidence of membrane protein transfer between hematopoietic cells (Cho and Hill, 2008;Yamanaka et al, 2009). Here, we carefully dissect events with parental marker coexpression and present evidence of hematopoietic 'homotypic' cell fusion (i.e.…”

In Vivo Chimera Model: Creation of Primary and Secondary Chimera

“…Unexpectedly, the authors observed the presence of mouse MHC class I protein on the surface of almost all human cells, suggesting that this mechanism was adopted by the human cells to evade host immune surveillance [ 60 ]. Follow up study by Chow T et al showed that transfer of MHC Class I from host to the donor cells plays an important role in protecting donor cells from NK cell and macrophage mediated rejection during hematopoietic stem cell transplantation and engraftment [ 61 ].…”