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.

Figure 1

Epicardial coronary arteries with AV showing distinct patterns of B cell and plasma cell infiltrates. A–C; Immunohistochemistry staining with CD20 showing B cell infiltrates as adventitial nodules (A–C), diffuse adventitial infiltrates (B), or neointimal infiltrates (A). D; Immunohistochemistry staining with syndecan-1 showing plasma cell infiltrates in the sclerotic adventitia. A–D; 2X. Insets; 20X.

Figure 2

Epicardial coronary artery with AV and adventitial nodular mononuclear cell infiltrates showing compartmentalization of B and T lymphocytes as well as plasma cells. Serial sections are stained by immunoperoxidase for B lymphocytes (CD20; A&B), T lymphocytes (CD3; C) and plasma cells (syndecan-1; D). (Magnification: A; 2X and B–D; 20X) * = arteriole.

Figure 3

Immunohistochemistry stains of C4d deposition and CXCL13 in patients with AV. C4d deposits are shown on the endothelium of a coronary artery with AV (A) and capillaries of adjacent myocardium (B). Lymphoid nodules stained for C4d (C), CXCL13 (D), B cells (CD20; E), and T cells (CD3; F). (Magnification: A −40X; B–D −20X; Insets − 60X)