• B cells;
  • cardiac allograft;
  • major histocompatibility complex class II;
  • mice;
  • protein kinase C theta


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.