Antibody deposition in rat heart which develops transplant vasculopathy in (donor x recipient) F1 environment.

Abstract

We studied the gene expression in rat cardiac allografts retransplanted into (donor x recipient) F1 animals to identify unknown or unexpected genes whose expression might contribute to the progression of transplant vasculopathy. Gene expression was first studied using a mRNA differential display, then it was further investigated using quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. We found that the rat immunoglobulin kappa chain gene was preferentially induced in retransplanted cardiac allografts in which transplant vasculopathy was developing. The diseased vessels in the same allografts were heavily infiltrated with CD45R-positive B cells. The expression of two genes related to B-cell responses, B-lymphocyte chemoattractant, and CD40 ligand, showed a similar time course to that of the immunoglobulin kappa chain gene. We observed a heavy deposit of both IgM and IgG on the pathological neointima late in the development of transplant vasculopathy (i.e., 30 days after retransplantation) that was absent from the allografts immediately after retransplantation. During the development of transplant vasculopathy in a (donor x recipient) F1 environment, B cells were selectively recruited into the allografts and stimulated; meanwhile, antibodies against the pathological neointima were formed. These antibodies may be involved in the pathogenesis of transplant vasculopathy.