BCR signaling is required for posttransplant lymphoproliferative disease in immunodeficient mice receiving human B cells

Authors: Ting-ting Zhang, Rene Yu-Hong Cheng, Andee R. Ott, Noelle P. Dahl, Emmaline R. Suchland, Claire M. Stoffers, Gregory D. Asher, Deyin Hou, Christopher D. Thouvenel, Tyler F. Hill, David J. Rawlings, Richard G. James

Published: 2024-04-10

DOI: 10.1126/scitranslmed.adh8846

Source: Full article


Abstract

Posttransplant lymphoproliferative disease (PTLD) is a major therapeutic challenge that has been difficult to study using human cells because of a lack of suitable models for mechanistic characterization. Here, we show that ex vivo–differentiated B cells isolated from a subset of healthy donors can elicit pathologies similar to PTLD when transferred into immunodeficient mice. The primary driver of PTLD-like pathologies were IgM-producing plasmablasts with Epstein-Barr virus (EBV) genomes that expressed genes commonly associated with EBV latency. We show that a small subset of EBV