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

Wenwei Yan, Rui Xu, Lian Li Ma, Wei Han, Sunil K. Geevarghese, Phillip E. Williams, Roger Sciammas, Anita S. Chong, Deng Ping Yin

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)919-927
Number of pages9
JournalTransplant International
Volume26
Issue number9
DOIs
StatePublished - Sep 2013
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Transplantation

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  • Cite this

    Yan, W., Xu, R., Ma, L. L., Han, W., Geevarghese, S. K., Williams, P. E., Sciammas, R., Chong, A. S., & Yin, D. P. (2013). B cells assist allograft rejection in the deficiency of protein kinase c-theta. Transplant International, 26(9), 919-927. https://doi.org/10.1111/tri.12143