Premium
B cell clonal expansion within immune infiltrates in human cardiac allograft vasculopathy
Author(s) -
Moore Carolina,
Gao Baoshan,
Roskin Krishna M.,
Vasilescu ElenaRodica M.,
Addonizio Linda,
Givertz Michael M.,
Madsen Joren C.,
Zorn Emmanuel
Publication year - 2020
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.15737
Subject(s) - antibody , b cell , cell , immune system , complementarity determining region , biology , pathology , somatic cell , medicine , immunology , immunoglobulin light chain , gene , genetics
Cardiac allograft vasculopathy (CAV) is associated with intragraft B cell infiltrates. Here, we studied the clonal composition of B cell infiltrates using 4 graft specimens with CAV. Using deep sequencing, we analyzed the immunoglobulin heavy chain variable region repertoire in both graft and blood. Results showed robust B cell clonal expansion in the graft but not in the blood for all cases. Several expanded B cell clones, characterized by their uniquely rearranged complementarity‐determining region 3, were detected in different locations in the graft. Sequences from intragraft B cells also showed elevated levels of mutated rearrangements in the graft compared to blood B cells. The number of somatic mutations per rearrangement was also higher in the graft than in the blood, suggesting that B cells continued maturing in situ. Overall, our studies demonstrated B cell clonal expansion in human cardiac allografts with CAV. This local B cell response may contribute to the pathophysiology of CAV through a mechanism that needs to be identified.