title: B cells mediate chronic allograft rejection independently of antibody production.
abstract: Chronic rejection is the primary cause of long-term failure of transplanted organs and is often viewed as an antibody-dependent process. Chronic rejection, however, is also observed in mice and humans with no detectable circulating alloantibodies, suggesting that antibody-independent pathways may also contribute to pathogenesis of transplant rejection. Here, we have provided direct evidence that chronic rejection of vascularized heart allografts occurs in the complete absence of antibodies, but requires the presence of B cells. Mice that were deficient for antibodies but not B cells experienced the same chronic allograft vasculopathy (CAV), which is a pathognomonic feature of chronic rejection, as WT mice; however, mice that were deficient for both B cells and antibodies were protected from CAV. B cells contributed to CAV by supporting splenic lymphoid architecture, T cell cytokine production, and infiltration of T cells into graft vessels. In chimeric mice, in which B cells were present but could not present antigen, both T cell responses and CAV were markedly reduced. These findings establish that chronic rejection can occur in the complete absence of antibodies and that B cells contribute to this process by supporting T cell responses through antigen presentation and maintenance of lymphoid architecture.
authors: Qiang
authors: Q
authors: Zeng
authors: Yue-Harn
authors: YH
authors: Ng
authors: Tripti
authors: T
authors: Singh
authors: Ke
authors: K
authors: Jiang
authors: Khaleefathullah A
authors: KA
authors: Sheriff
authors: Renee
authors: R
authors: Ippolito
authors: Salwa
authors: S
authors: Zahalka
authors: Qi
authors: Q
authors: Li
authors: Parmjeet
authors: P
authors: Randhawa
authors: Rosemary A
authors: RA
authors: Hoffman
authors: Balathiripurasundari
authors: B
authors: Ramaswami
authors: Frances E
authors: FE
authors: Lund
authors: Geetha
authors: G
authors: Chalasani
mesh_terms: D064591:Allografts / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009206:Myocardium / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines