B cells assist allograft rejection in the deficiency of protein kinase c-theta.

We have previously shown that mice deficient in protein kinase C theta (PKC) 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 PKC. Mouse cardiac allograft transplantations were performed from Balb/c (H-2d) to PKC knockout (PKC-/-), PKC 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-B activation in the donor cardiac allograft. Anti-B cell antibody (rituximab) significantly delayed allograft rejection in PKC-/-, but not in WT mice. Co-transfer of PKC-/- T plus PKC-/- 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 PKC-/- and CD28(-/-) double-deficient (PCDK) mice to acutely reject allografts, suggested that an effective cognate interaction between PKC-/- T and B cells for acute rejection is CD28 molecule dependent. We conclude that T-B cell interactions synergize with PKC-/- T cells to mediate acute allograft rejection.