Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease.

Abstract

Chronic graft-versus-host disease (cGVHD) causes significant morbidity and mortality in patients otherwise cured of malignancy after hematopoietic stem cell transplantation (HSCT). The presence of alloantibodies and high plasma B cell-activating factor (BAFF) levels in patients with cGVHD suggest that B cells play a role in disease pathogenesis. We performed detailed phenotypic and functional analyses of peripheral B cells in 82 patients after HSCT. Patients with cGVHD had significantly higher BAFF/B-cell ratios compared with patients without cGVHD or healthy donors. In cGVHD, increasing BAFF concentrations correlated with increased numbers of circulating pre-germinal center (GC) B cells and post-GC "plasmablast-like" cells, suggesting in vivo BAFF dependence of these 2 CD27(+) B-cell subsets. Circulating CD27(+) B cells in cGVHD comprised in vivo activated B cells capable of IgG production without requiring additional antigen stimulation. Serial studies revealed that patients who subsequently developed cGVHD had delayed reconstitution of naive B cells despite persistent BAFF elevation as well as proportional increase in CD27(+) B cells in the first year after HSCT. These studies delineate specific abnormalities of B-cell homeostasis in patients with cGVHD and suggest that BAFF targeting agents may be useful in this disease.

• Authors: Stefanie Sarantopoulos, Kristen E Stevenson, Haesook T Kim, Corey S Cutler, Nazmim S Bhuiya, Michael Schowalter, Vincent T Ho, Edwin P Alyea, John Koreth, Bruce R Blazar, Robert J Soiffer, Joseph H Antin, Jerome Ritz
• Journal: Blood (Blood) Vol. 113 Issue 16 Pg. 3865-74 (Apr 16 2009) ISSN: 1528-0020 [Electronic] United States
• PMID: 19168788 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• B-Cell Activating Factor
• Immunoglobulin G
• Isoantibodies
• TNFSF13B protein, human
• Tumor Necrosis Factor Receptor Superfamily, Member 7

Topics

• Adult
• Aged
• B-Cell Activating Factor (blood, immunology)
• B-Lymphocyte Subsets (immunology, pathology)
• Chronic Disease
• Female
• Follow-Up Studies
• Graft vs Host Disease (blood, immunology, mortality, pathology, therapy)
• Hematologic Neoplasms (immunology, mortality, pathology, therapy)
• Hematopoietic Stem Cell Transplantation
• Homeostasis (immunology)
• Humans
• Immunoglobulin G (blood, immunology)
• Isoantibodies (blood, immunology)
• Male
• Middle Aged
• Retrospective Studies
• Transplantation, Homologous
• Tumor Necrosis Factor Receptor Superfamily, Member 7 (immunology, metabolism)