title: Acquisition of humoral transplantation tolerance upon de novo emergence of B lymphocytes.
abstract: A major obstacle to transplantation tolerance is humoral immunity. In this paper, we demonstrate that the intrinsic developmental propensity of the B lymphocyte compartment for acquisition of self-tolerance can be harnessed to induce humoral unresponsiveness to transplanted alloantigens. In the current study, when transitional B cells developed in the presence of donor lymphoid cells, the mature B lymphocyte compartment failed to mount a donor-specific alloantibody response to an organ transplant--despite unrestrained acute T cell-mediated allograft rejection. Specifically, we generated an experimental system wherein a B6 strain B cell compartment developed de novo in the presence of F1 (B6xBALB/c) lymphoid cells and in a T cell-deficient setting. Following establishment of a steady-state B cell compartment, these B6 mice were transplanted with heterotopic cardiac allografts from allogeneic BALB/c donors. The mice were then inoculated with purified syngeneic B6 T cells. As expected, all cardiac allografts were acutely rejected. However, the B lymphocyte compartment of these mice was completely inert in its capacity to form a BALB/c-specific alloantibody response. Using an alloantigen-specific Ig transgenic system, we demonstrated that this profound degree of humoral tolerance was caused by clonal deletion of alloreactive specificities from the primary B cell repertoire. Thus, de novo B cell compartment development at the time of transplantation is of critical importance in recipient repertoire "remodeling" to a humoral tolerant state.
authors.affiliation: Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Parsons
authors.forename: Kumar
authors.initials: K
authors.lastname: Vivek
authors.forename: Susan Y
authors.initials: SY
authors.lastname: Rostami
authors.forename: Ghazal
authors.initials: G
authors.lastname: Zekavat
authors.forename: Seyed M
authors.initials: SM
authors.lastname: Ziaie
authors.forename: Yanping
authors.initials: Y
authors.lastname: Luo
authors.forename: Brigitte
authors.initials: B
authors.lastname: Koeberlein
authors.forename: Robert R
authors.initials: RR
authors.lastname: Redfield
authors.forename: Michael P
authors.initials: MP
authors.lastname: Cancro
authors.forename: Ali
authors.initials: A
authors.lastname: Naji
authors.forename: Hooman
authors.initials: H
authors.lastname: Noorchashm
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000918:Antibody Specificity / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000637:transplantation; D016026:Bone Marrow Transplantation / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002999:Clone Cells; D016027:Heart Transplantation / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D007518:Isoantibodies / Q000096:biosynthesis*; D007519:Isoantigens / Q000235:genetics / Q000276:immunology; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D016038:Skin Transplantation / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation; D023001:Transplantation Tolerance / Q000235:genetics
chemical_list: D007518:Isoantibodies; D007519:Isoantigens