Bone marrow T-cell infiltration during acute GVHD is associated with delayed B-cell recovery and function after HSCT.
B-cell immune dysfunction contributes to the risk of severe infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Delayed B-cell regeneration is found in patients with systemic graft-versus-host disease (GVHD) and is often accompanied by bone marrow (BM) suppression. Little is known about human BM GVHD. We analyzed the reconstitution kinetics of B-cell subsets in adult leukemic patients within 6 months after allo-HSCT. B-cell deficiency already existed before transplant and was aggravated after transplant. Onset of B-cell reconstitution characterized by transitional B-cell recovery occurred either early (months 2-3) or late (from month 6 on) and correlated highly positively with reverse transcription-polymerase chain reaction quantified numbers of κ-deleting recombination excision circles (KRECs). Delayed recovery was associated with systemic acute GVHD and full-intensity conditioning therapy. Histological analysis of BM trephines revealed increased T-cell infiltration in late recovering patients, which was associated with reduced numbers of osteoblasts. Functionally, late recovering patients displayed less pneumococcal polysaccharide-specific immunoglobin M-producing B cells on ex vivo B-cell activation than early recovering patients. Our results provide evidence for acute BM GVHD in allo-HSCT patients with infiltrating donor T cells and osteoblast destruction. This is associated with delayed B-cell reconstitution and impaired antibody response. Herein, KREC appears suitable to monitor BM B-cell output after transplant.
Institute for Medical Immunology, Charité University Medicine, Berlin, Germany; Experimental and Clinical Research Center, Berlin, Germany;
Angela
A
Mensen
Institute of Pathology.
Korinna
K
Jöhrens
Institute of Pathology.
Ioannis
I
Anagnostopoulos
Institute for Medical Immunology, Charité University Medicine, Berlin, Germany; Experimental and Clinical Research Center, Berlin, Germany;
Sonya
S
Demski
Institute for Medical Immunology, Charité University Medicine, Berlin, Germany;
Maike
M
Oey
Institute for Biometry and Clinical Epidemiology.
Andrea
A
Stroux
Department of Hematology, Oncology and Tumor Immunology, and.
Philipp
P
Hemmati
Department of Hematology, Oncology and Tumor Immunology, and.
Jörg
J
Westermann
Department of Hematology, Oncology and Tumor Immunology, and.
Olga
O
Blau
Department of Hematology, Oncology and Tumor Immunology, and.
Friedrich
F
Wittenbecher
Charité Stem Cell Facility, Charité University Medicine, Berlin, Germany; and.
Kamran
K
Movassaghi
Experimental and Clinical Research Center, Berlin, Germany;
Martin
M
Szyska
Institute for Medical Immunology, Charité University Medicine, Berlin, Germany;
Sybill
S
Thomas
Department of Hematology, Oncology and Tumor Immunology, and.
Bernd
B
Dörken
Institute for Medical Immunology, Charité University Medicine, Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany.
Carmen
C
Scheibenbogen
Department of Hematology, Oncology and Tumor Immunology, and.
Renate
R
Arnold
Institute for Medical Immunology, Charité University Medicine, Berlin, Germany; Experimental and Clinical Research Center, Berlin, Germany; Department of Hematology, Oncology and Tumor Immunology, and.
Il-Kang
IK
Na
D000208:Acute Disease; D000328:Adult; D000368:Aged; D064591:Allografts; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D005260:Female; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007938:Leukemia / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013997:Time Factors; D055815:Young Adult