title: Aged B cells alter immune regulation of allografts in mice.
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.
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.|Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Mori
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.|Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.|Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Anjela
authors.initials: A
authors.lastname: Galan
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA. drgoldst@med.umich.edu.|Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, MI, USA. drgoldst@med.umich.edu.|Institute of Gerontology, University of Michigan, Ann Arbor, MI, USA. drgoldst@med.umich.edu.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Goldstein
mesh_terms: D015720:5'-Nucleotidase / Q000235:genetics; D019264:Adoptive Transfer; D000375:Aging / Q000276:immunology*; D064591:Allografts / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D018122:B7-1 Antigen / Q000235:genetics; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation; D051195:Toll-Like Receptor 2 / Q000235:genetics; D014184:Transplantation, Homologous; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D019010:Vascular Cell Adhesion Molecule-1; D015720:5'-Nucleotidase
keywords: Aging; Animal models; B cells; Immune regulation; Transplantation