title: B cells and plasma cells in coronaries of chronically rejected cardiac transplants.
abstract: BACKGROUND.: Previously, we reported that transcripts of immunoglobulins were increased in coronary arteries dissected from cardiac transplants with arteriopathy, but the prevelance and patterns of B cell and plasma cell infiltration in cardiac allografts has not been documented. METHODS.: In this study, we documented the frequency and distribution of B cells and plasma cells in 16 cardiac transplants with advanced chronic rejection that were explanted during a second transplant procedure. Coronary arteries with pathologically confirmed allograft vasculopathy and controls with native atherosclerosis were immunohistologically stained for markers of T cells, B cells, plasma cells, IgG subclasses, C4d, CD21, and CXCL13. RESULTS.: We found that B cells and plasma cells were prevalent in most of the samples analyzed (14 of 16) and were distributed in three patterns: adventitial nodules, diffuse adventitial infiltrates, and neointimal infiltrates. These cells were found most frequently in nodules, some of which had distinct compartmentalization and granular C4d deposits on follicular dendritic cells (FDCs) that typify tertiary lymphoid nodules. FDCs also stained for CD21 and CXCL13. Diffuse infiltrates of B cells and plasma cells were found in fibrotic areas of the neointima and adventitia. Only a minority of control coronaries with atherosclerosis contained B cells. CONCLUSIONS.: B cells and plasma cell infiltrates are consistent findings in and around coronary arteries with allograft vasculopathy and are significantly more frequent than in coronaries with native atherosclerosis. The presence of C4d on FDCs in tertiary lymphoid nodules suggests active antigen presentation.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. wehnerj@ccf.org
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Wehner
authors.forename: Karen
authors.initials: K
authors.lastname: Fox-Talbot
authors.forename: Marc K
authors.initials: MK
authors.lastname: Halushka
authors.forename: Carla
authors.initials: C
authors.lastname: Ellis
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Zachary
authors.forename: William M
authors.initials: WM
authors.lastname: Baldwin
mesh_terms: D000328:Adult; D000906:Antibodies / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D002908:Chronic Disease; D003327:Coronary Disease / Q000235:genetics / Q000276:immunology; D003331:Coronary Vessels / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000601:surgery; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology*; D012086:Reoperation; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000906:Antibodies; D007136:Immunoglobulins
references.citation: Am J Transplant. 2005 Mar;5(3):510-6
references.pmid: 15707405
references.citation: Am J Pathol. 2009 Feb;174(2):693-700
references.pmid: 19131590
references.citation: Nat Rev Immunol. 2006 Jul;6(7):508-19
references.pmid: 16778830
references.citation: Clin Transplant. 1994 Jun;8(3 Pt 2):289-92
references.pmid: 8061370
references.citation: Am J Transplant. 2007 Jan;7(1):201-10
references.pmid: 17061985
references.citation: Transplantation. 2006 Dec 27;82(12):1769-73
references.pmid: 17198274
references.citation: J Immunol. 2001 Jul 15;167(2):1072-80
references.pmid: 11441118
references.citation: Immunity. 2001 Apr;14(4):387-97
references.pmid: 11336684
references.citation: J Heart Lung Transplant. 2005 Nov;24(11):1710-20
references.pmid: 16297770
references.citation: Am J Transplant. 2005 Sep;5(9):2248-52
references.pmid: 16095505
references.citation: Transpl Immunol. 2008 Jul;19(3-4):209-14
references.pmid: 18617005
references.citation: Transplantation. 1992 Jun;53(6):1169-79
references.pmid: 1604469
references.citation: Pathol Res Pract. 2007;203(3):163-7
references.pmid: 17307308
references.citation: J Heart Lung Transplant. 2008 Sep;27(9):943-56
references.pmid: 18765186
references.citation: Am J Transplant. 2007 Aug;7(8):1968-73
references.pmid: 17617861
references.citation: Cardiovasc Pathol. 2004 Jul-Aug;13(4):233-6
references.pmid: 15210141
references.citation: J Heart Lung Transplant. 2009 Mar;28(3):255-9
references.pmid: 19285617
references.citation: Cardiovasc Pathol. 2005 Jul-Aug;14(4):219-24
references.pmid: 16009321
references.citation: Kidney Int. 2008 Sep;74(5):664-73
references.pmid: 18547992
references.citation: Circ Res. 2007 Feb 2;100(2):191-203
references.pmid: 17272820
references.citation: Transplantation. 2008 Jun 27;85(12):1705-14
references.pmid: 18580460
references.citation: Transplantation. 2008 Jun 15;85(11):1648-53
references.pmid: 18551073
references.citation: Kidney Int. 2008 Mar;73(5):533-7
references.pmid: 18094677
references.citation: Am J Pathol. 2007 Apr;170(4):1415-27
references.pmid: 17392180
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14723-8
references.pmid: 16192350
references.citation: Arch Pathol Lab Med. 1989 Jun;113(6):690-8
references.pmid: 2658911
references.citation: Transplant Proc. 2007 Mar;39(2):432-4
references.pmid: 17362749
references.citation: Am J Transplant. 2007 Apr;7(4):949-54
references.pmid: 17331114
references.citation: J Immunol. 2005 May 15;174(10):6161-8
references.pmid: 15879112
references.citation: Cardiovasc Pathol. 2005 Jul-Aug;14(4):176-80
references.pmid: 16009314
references.citation: Transplantation. 2008 Sep 27;86(6):772-8
references.pmid: 18813100
references.citation: Immunology. 1989 Feb;66(2):270-7
references.pmid: 2925226
references.citation: Am J Transplant. 2009 Jan;9(1):169-78
references.pmid: 18976290
references.citation: Mod Pathol. 1991 Sep;4(5):654-60
references.pmid: 1836878