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.
- B cells
- cardiac allograft
- major histocompatibility complex class II
- protein kinase C theta
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