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Eur J Immunol. 2016 Nov;46(11):2650-2658. doi: 10.1002/eji.201646353. Epub 2016 Sep 21.

Aged B cells alter immune regulation of allografts in mice.

Author information

1
Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
2
Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
3
Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
4
Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
5
Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA. drgoldst@med.umich.edu.
6
Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, MI, USA. drgoldst@med.umich.edu.
7
Institute of Gerontology, University of Michigan, Ann Arbor, MI, USA. drgoldst@med.umich.edu.

Abstract

Organ transplantation in older people is increasing, but how aging impacts B-cell responses to organ transplantation is still unknown. Here, we show that the depletion of B cells with anti-CD20 antibodies has disparate effects depending on recipient age. In young murine recipients, anti-CD20 treatment impaired the ability of immune modulation to extend skin allograft survival. In contrast, anti-CD20 treatment extended allograft survival in aged recipients treated with immune modulation. Although regulatory B-cell function and the numbers of marginal and follicular B cells were similar between age groups, a subpopulation of B cells, termed age-associated B cells (ABCs), accumulated upon aging. ABCs isolated from aged mice exhibited upregulation of CD73, CD80, CD106, and TLR2 and an increased capacity to augment T-cell alloimmunity compared to ABCs from young mice. Importantly, ABCs from aged, but not young, mice impaired the ability of immune modulation to enhance allograft survival after adoptive transfer into young transplant recipients. Our study indicates that ABCs impair the immune regulation of allografts. Thus, recipient age needs to be considered when proposing B-cell-depleting immune therapy.

KEYWORDS:

Aging; Animal models; B cells; Immune regulation; Transplantation

PMID:
27546296
PMCID:
PMC5366259
[Available on 2017-11-01]
DOI:
10.1002/eji.201646353
[Indexed for MEDLINE]
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