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 language | English (US) |
|---|---|
| Pages (from-to) | 919-927 |
| Number of pages | 9 |
| Journal | Transplant International |
| Volume | 26 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 2013 |
| Externally published | Yes |
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Keywords
- B cells
- cardiac allograft
- major histocompatibility complex class II
- mice
- protein kinase C theta
ASJC Scopus subject areas
- Transplantation
Cite this
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 journal › Article
}
TY - JOUR
T1 - B cells assist allograft rejection in the deficiency of protein kinase c-theta
AU - Yan, Wenwei
AU - Xu, Rui
AU - Ma, Lian Li
AU - Han, Wei
AU - Geevarghese, Sunil K.
AU - Williams, Phillip E.
AU - Sciammas, Roger
AU - Chong, Anita S.
AU - Yin, Deng Ping
PY - 2013/9
Y1 - 2013/9
N2 - 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.
AB - 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.
KW - B cells
KW - cardiac allograft
KW - major histocompatibility complex class II
KW - mice
KW - protein kinase C theta
UR - http://www.scopus.com/inward/record.url?scp=84882453478&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84882453478&partnerID=8YFLogxK
U2 - 10.1111/tri.12143
DO - 10.1111/tri.12143
M3 - Article
C2 - 23841454
AN - SCOPUS:84882453478
VL - 26
SP - 919
EP - 927
JO - Transplant International
JF - Transplant International
SN - 0934-0874
IS - 9
ER -