title: Contribution of donor-specific antibodies to acute allograft rejection: evidence from B cell-deficient mice.
abstract: BACKGROUND
  The role of T lymphocytes in acute allograft rejection is well established. The involvement of B lymphocytes in this process, however, is more controversial. A series of reports showed that mice without a functional B-cell compartment rejected allografts with the same kinetics as control animals. In rats, however, alloantibodies were found to play a decisive role in allograft rejection. To provide an explanation for the discrepant results, we readdressed the role of B cells and antibodies in mice with disrupted immunoglobulin mu chain genes. The use of cyclosporine (CsA), which strongly suppresses T cells, allowed us to focus specifically on the function of B cells.
  
  
  METHODS
  C57BL/6 mice rendered B cell deficient by targeted disruption of the immunoglobulin mu chain gene (referred to as microMT/microMT mice) and microMT/+ control mice with one functional mu chain were heterotopically transplanted with fully MHC-disparate BALB/c hearts. CsA was administered subcutaneously by Alzet osmotic pumps. Normal and immune serum specific for donor hearts was given to assess the role of antibodies in the rejection process.
  
  
  RESULTS
  Both B cell-deficient microMT/microMT and heterozygous microMT/+ mice were found to reject transplanted hearts within a similar period of time. In contrast, when T cells were partially suppressed with CsA, graft survival was significantly prolonged in microMT/microMT mice as compared with heterozygous controls. Passive transfer of donor-specific immune serum, obtained from microMT/+ animals rejecting allogeneic hearts, to CsA-treated microMT/microMT mice significantly accelerated allograft rejection as opposed to recipients treated with normal serum.
  
  
  CONCLUSIONS
  B lymphocytes and antibodies play an important role in acute allograft rejection particularly when the dominant T-cell compartment is partially suppressed.
authors.affiliation: Novartis Pharma Research, Basel, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Brändle
authors.forename: J
authors.initials: J
authors.lastname: Joergensen
authors.forename: G
authors.initials: G
authors.lastname: Zenke
authors.forename: K
authors.initials: K
authors.lastname: Bürki
authors.forename: R P
authors.initials: RP
authors.lastname: Hof
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D016572:Cyclosporine / Q000494:pharmacology; D018390:Gene Targeting; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D007106:Immune Sera / Q000276:immunology; D007074:Immunoglobulin G / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007518:Isoantibodies / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008810:Mice, Inbred C57BL / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D007106:Immune Sera; D007074:Immunoglobulin G; D007148:Immunoglobulin mu-Chains; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D016572:Cyclosporine