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.

The generation and maintenance of serum alloantibody

“…Plasma cells have also been described in inflamed tissues for example, in the joints of patients with rheumatoid arthritis, the thymi of those with myasthenia gravis and the kidneys of those with SLE, suggesting that inflammatory lesions may provide supplementary survival niches. Similarly, plasma cells have also been described in renal and cardiac allograft [21-23]. …”

Interacting Mechanisms in the Pathogenesis of Cardiac Allograft Vasculopathy

“…The expanded intima contains microvessels and an infiltrate formed largely of host T cells and macrophages 10, 12 and a majority of the T cells are memory cells that express IFN-γ and TGF-β 13 . Nodular aggregrates of host B cells, T cells and myeloid cells are commonly found in the adventitia, possibly as part of rudimentary tertiary lymphoid organs associated with chronic inflammation 14 . The media appears generally normal in arteries affected by CAV.…”

Cardiac allograft vasculopathy: do adipocytes bridge alloimmune and metabolic risk factors?

“…Differences in amounts and inflammatory state of epicardial fat may also explain the clinical risk for CAV associated with hearts from older male donors [1 ]. The proinflammatory environment provided by epicardial fat may also support the intense mononuclear cell infiltrates observed in the periadventitial fat of human cardiac transplants with advanced CAV [26]. These infiltrates contain large numbers of T cells, B cells and plasma The coronary is embedded in epicardial adipose tissue on the surface of the heart separated from the cardiomyocytes.…”

“…1). The inflammatory and mesenchymal composition of the intimal lesion has been characterized extensively [25,26]. Inflammatory leukocytes and fibroblasts have also been described in the adventitia, but the influence of epicardial fat on the development of CAV has not been examined even though recent evidence indicates that perivascular adipose tissue modulates other forms of vascular remodeling.…”