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Eur J Immunol. 2015 Mar;45(3):843-53. doi: 10.1002/eji.201445082. Epub 2014 Dec 16.

Transitional-2 B cells acquire regulatory function during tolerance induction and contribute to allograft survival.

Author information

1
MRC Centre for Transplantation, King's College London Guy's Hospital, London, UK.

Abstract

In humans, tolerance to renal transplants has been associated with alterations in B-cell gene transcription and maintenance of the numbers of circulating transitional B cells. Here, we use a mouse model of transplantation tolerance to investigate the contribution of B cells to allograft survival. We demonstrate that transfer of B cells from mice rendered tolerant to MHC class I mismatched skin grafts can prolong graft survival in a dose-dependent and antigen-specific manner to a degree similar to that afforded by graft-specific regulatory T (Treg) cells. Tolerance in this model was associated with an increase in transitional-2 (T2) B cells. Only T2 B cells from tolerized mice, not naïve T2 nor alloantigen experienced T2, were capable of prolonging skin allograft survival, and suppressing T-cell activation. Tolerized T2 B cells expressed lower levels of CD86, increased TIM-1, and demonstrated a preferential survival in vivo. Furthermore, we demonstrate a synergistic effect between tolerized B cells and graft-specific Treg cells. IL-10 production by T2 B cells did not contribute to tolerance, as shown by transfer of B cells from IL-10(-/-) mice. These results suggest that T2 B cells in tolerant patients may include a population of regulatory B cells that directly inhibit graft rejection.

KEYWORDS:

Regulatory B cells; Regulatory T cells; T2 B cells; Tolerance; Transplantation

PMID:
25408265
DOI:
10.1002/eji.201445082
[Indexed for MEDLINE]
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