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

Fingerprint

Protein Kinases
Protein Kinase C
Allografts
B-Lymphocytes
T-Lymphocytes
Proto-Oncogene Proteins c-akt
Heart Transplantation
Major Histocompatibility Complex
Inbred C57BL Mouse
Cell Communication
Antibodies

Keywords

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

ASJC Scopus subject areas

  • Transplantation

Cite this

Yan, W., Xu, R., Ma, L. L., Han, W., Geevarghese, S. K., Williams, P. E., ... 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

B cells assist allograft rejection in the deficiency of protein kinase c-theta. / Yan, Wenwei; Xu, Rui; Ma, Lian Li; Han, Wei; Geevarghese, Sunil K.; Williams, Phillip E.; Sciammas, Roger; Chong, Anita S.; Yin, Deng Ping.

In: Transplant International, Vol. 26, No. 9, 09.2013, p. 919-927.

Research output: Contribution to journalArticle

Yan, W, Xu, R, Ma, LL, Han, W, Geevarghese, SK, Williams, PE, Sciammas, R, Chong, AS & Yin, DP 2013, 'B cells assist allograft rejection in the deficiency of protein kinase c-theta', Transplant International, vol. 26, no. 9, pp. 919-927. https://doi.org/10.1111/tri.12143
Yan W, Xu R, Ma LL, Han W, Geevarghese SK, Williams PE et al. B cells assist allograft rejection in the deficiency of protein kinase c-theta. Transplant International. 2013 Sep;26(9):919-927. https://doi.org/10.1111/tri.12143
Yan, Wenwei ; Xu, Rui ; Ma, Lian Li ; Han, Wei ; Geevarghese, Sunil K. ; Williams, Phillip E. ; Sciammas, Roger ; Chong, Anita S. ; Yin, Deng Ping. / B cells assist allograft rejection in the deficiency of protein kinase c-theta. In: Transplant International. 2013 ; Vol. 26, No. 9. pp. 919-927.
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