Reconstitution of Allogeneic Hemopoietic Stem Cells: The Essential Role of FcRγ and the TCR β-Chain-FCp33 Complex

Abstract

Transplantation of purified allogeneic hemopoietic stem cells (SC) alone is characterized by a decreased risk of graft-vs-host disease but increased incidence of engraftment failure. It has been established that the facilitating cell (FC) promotes allogeneic SC reconstitution and results in donor-specific transplantation tolerance across MHC disparities, without graft-vs-host disease. Although the requirements for this facilitating function are not well-characterized, it is known that facilitation is dependent on FC expression of a unique heterodimer consisting of the TCR β-chain (TCRβ) and a 33-kDa protein, FCp33. The current study confirms that CD3ε and TCRβ expression are present on the FC at the time of transplantation and demonstrates that the majority of cells in the FC population express the TCR signaling molecule, FcRγ, rather than the more conventional CD3ζ receptor. Of particular significance, we have now demonstrated that FC-mediated allogeneic SC reconstitution is critically dependent on FcRγ expression and that FcRγ coprecipitates with the TCRβ-FCp33 heterodimer. The mandatory requirement of TCRβ and FcRγ for FC function provides the first evidence of a previously undescribed role for FcRγ in the facilitation of allogeneic SC reconstitution and establishes that FcRγ is part of the TCRβ-FCp33 complex uniquely expressed on FC.