Monoclonal antibody analysis of canine hemopoietic cells. Role of Ia-like and Thy-1 antigens in bone marrow engraftment.
The expression of Ia-like (class II MHC) antigens on canine hemopoietic cells was investigated using a cytotoxic murine monoclonal antibody, WM-2, reactive with dog Ia-like antigens. Another monoclonal antibody, WMD-1, reactive with canine Thy-1 antigen, was used as a positive control. Depletion of Ia+ cells from dog bone marrow by complement-mediated lysis with WM-2 antibody failed to inhibit growth of granulocyte-macrophage progenitors (CFUGM) in vitro, while WMD-1 produced complete inhibition of CFUGM. Lethally irradiated dogs receiving bone marrow autografts depleted of Ia-positive cells ex vivo showed initial engraftment, followed by prolonged pancytopenia, and eventual complete recovery of marrow function in the majority of animals. In contrast, dogs receiving autografts treated with WMD-1 and complement all died of marrow failure. We interpret these results as indicating: (1) that Thy-1 antigen is present on hemopoietic stem cells essential for marrow engraftment; and (2) that the expression of Ia antigens on hemopoietic cells is heterogeneous and related to the level of stem cell maturation. While Ia appears to be present on a stem cell population at an earlier stage than CFUGM, as evidenced by the transient phase of graft failure seen in dogs receiving Ia-depleted marrow, the most primitive stem cell, responsible for long-term engraftment, is effectively Ia-negative.
Prendergast
M M
MM
Bradstock
K F
KF
Broomhead
A F
AF
Hughes
W G
WG
Kabral
A
A
Berndt
M C
MC
Tiver
K
K
D000818:Animals; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D003114:Colony-Forming Units Assay; D003165:Complement System Proteins / Q000276:immunology; D004285:Dogs; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D018800:Thy-1 Antigens
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000949:Histocompatibility Antigens Class II; D018800:Thy-1 Antigens; D003165:Complement System Proteins