B cells in chronic graft-versus-host disease.

Journal Article (Journal Article;Review)

Allogeneic hematopoietic stem cell transplantation (alloHCT) is the definitive therapy for numerous otherwise incurable hematologic malignancies and non-malignant diseases. The genetic disparity between donor and recipient both underpins therapeutic effects and confers donor immune system-mediated damage in the recipient, called graft-versus-host disease (GVHD). Chronic GVHD (cGVHD) is a major cause of late post-transplant morbidity and mortality. B cells have a substantiated role in cGVHD pathogenesis, as first demonstrated by clinical response to the anti-CD20 monoclonal antibody, rituximab. Initiation of CD20 blockade is met at times with limited therapeutic success that has been associated with altered peripheral B cell homeostasis and excess B Cell Activating Factor of the TNF family (BAFF). Increased BAFF to B cell ratios are associated with the presence of circulating, constitutively activated B cells in patients with cGVHD. These cGVHD patient B cells have increased survival capacity and signal through both BAFF-associated and B Cell Receptor (BCR) signaling pathways. Proximal BCR signaling molecules, Syk and BTK, appear to be hyper-activated in cGVHD B cells and can be targeted with small molecule inhibitors. Murine studies have confirmed roles for Syk and BTK in development of cGVHD. Emerging evidence has prompted investigation of several small molecule inhibitors in an attempt to restore B cell homeostasis and potentially target rare, pathologic B cell populations.

Full Text

Duke Authors

Cited Authors

  • McManigle, W; Youssef, A; Sarantopoulos, S

Published Date

  • June 2019

Published In

Volume / Issue

  • 80 / 6

Start / End Page

  • 393 - 399

PubMed ID

  • 30849450

Pubmed Central ID

  • PMC8049519

Electronic International Standard Serial Number (EISSN)

  • 1879-1166

Digital Object Identifier (DOI)

  • 10.1016/j.humimm.2019.03.003


  • eng

Conference Location

  • United States