title: B cells assist allograft rejection in the deficiency of protein kinase c-theta.
abstract: We have previously shown that mice deficient in protein kinase C theta (PKCθ) have the ability to reject cardiac allografts, but are susceptible to tolerance induction. Here we tested role of B cells in assisting alloimmune responses in the absence of PKCθ. Mouse cardiac allograft transplantations were performed from Balb/c (H-2d) to PKCθ knockout (PKCθ(-/-)), PKCθ and B cell double-knockout (PBDK, H-2b) mice and wild-type (WT) C57BL/6 (H-2b) mice. PBDK mice spontaneously accepted the allografts with the inhibition of NF-κB activation in the donor cardiac allograft. Anti-B cell antibody (rituximab) significantly delayed allograft rejection in PKCθ(-/-), but not in WT mice. Co-transfer of PKCθ(-/-) T plus PKCθ(-/-) B cells or primed sera triggered allograft rejection in Rag1(-/-) mice, and only major histocompatibility complex class II-enriched B cells, but not class I-enriched B cells, were able to promote rejection. This, together with the inability of PKCθ(-/-) and CD28(-/-) double-deficient (PCDK) mice to acutely reject allografts, suggested that an effective cognate interaction between PKCθ(-/-) T and B cells for acute rejection is CD28 molecule dependent. We conclude that T-B cell interactions synergize with PKCθ(-/-) T cells to mediate acute allograft rejection.
authors.affiliation: Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Yan
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.forename: Lian Li
authors.initials: LL
authors.lastname: Ma
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Geevarghese
authors.forename: Phillip E
authors.initials: PE
authors.lastname: Williams
authors.forename: Roger
authors.initials: R
authors.lastname: Sciammas
authors.forename: Anita S
authors.initials: AS
authors.lastname: Chong
authors.forename: Deng Ping
authors.initials: DP
authors.lastname: Yin
mesh_terms: D064591:Allografts; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology*; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology*; D016027:Heart Transplantation; D007527:Isoenzymes / Q000172:deficiency* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000172:deficiency* / Q000276:immunology; D000074121:Protein Kinase C-theta; D000069283:Rituximab; D013601:T-Lymphocytes / Q000637:transplantation
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007527:Isoenzymes; D016328:NF-kappa B; D000069283:Rituximab; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta
keywords: B cells; cardiac allograft; major histocompatibility complex class II; mice; protein kinase C theta