Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease.
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.
Sarantopoulos
Stefanie
S
Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. stefanie_sarantopoulos@dfci.harvard.edu
Stevenson
Kristen E
KE
Kim
Haesook T
HT
Cutler
Corey S
CS
Bhuiya
Nazmim S
NS
Schowalter
Michael
M
Ho
Vincent T
VT
Alyea
Edwin P
EP
Koreth
John
J
Blazar
Bruce R
BR
Soiffer
Robert J
RJ
Antin
Joseph H
JH
Ritz
Jerome
J
D000328:Adult; D000368:Aged; D053264:B-Cell Activating Factor / Q000097:blood / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology* / Q000378:metabolism
D053264:B-Cell Activating Factor; D007074:Immunoglobulin G; D007518:Isoantibodies; C505719:TNFSF13B protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7