Characterization of memory B cells from thymus and its impact for DLBCL classification.
The rare memory B cells in thymus (Thy) are considered the cells of origin for primary mediastinal large B-cell lymphoma. The objectives of the present study were to characterize the normal memory B-cell compartment in Thy and to support its association with primary mediastinal B-cell lymphoma. Seven paired human tissue samples from Thy and sternum bone marrow (BM) were harvested during cardiac surgery. B-cell subsets were phenotyped by Euroflow standard and fluorescence-activated cell sorting for microarray analysis on the Human Exon 1.0 ST Arrays platform. Differentially expressed genes between Thy and BM memory B cells were identified and correlated with the molecular subclasses of diffuse large B-cell lymphoma. Within Thy, 4% (median; range 2%-14%) of the CD45(+) hematopoietic cells were CD19(+) B cells, with a major fraction being CD27(+)/CD38(-) memory B cells (median 80%, range 76%-93%). The BM contained 14% (median; range 3%-27%), of which only a minor fraction (median 5%, range 2%-10%) were memory B cells. Global gene expression analysis of the memory B-cell subsets from the two compartments identified 133 genes upregulated in Thy, including AICDA, REL, STAT1, TNF family, SLAMF1, CD80, and CD86. In addition, exons 4 and 5 in the 3' end of AICDA were more highly expressed in Thy than in BM. The Thy memory B-cell gene profile was overexpressed in primary mediastinal B-cell lymphoma compared with other diffuse large B-cell lymphoma subclasses. The present study describes a Thy memory B-cell subset and its gene profile correlated with primary mediastinal B-cell lymphomas, suggesting origin from Thy memory B cells.
Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
Kim Steve
KS
Bergkvist
Department of Cardiothoracic Surgery, Aalborg University Hospital, Aalborg, Denmark.
Martin Agge
MA
Nørgaard
Department of Haematology, Aalborg University Hospital, Aalborg, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Martin
M
Bøgsted
Department of Haematology, Aalborg University Hospital, Aalborg, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
Alexander
A
Schmitz
Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
Mette
M
Nyegaard
Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Otolaryngology, Head and Neck Surgery, Aalborg University Hospital, Aalborg, Denmark.
Michael
M
Gaihede
Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
John
J
Bæch
Department of Vascular Surgery, Aalborg University Hospital, Aalborg, Denmark.
Marie-Louise
ML
Grønholdt
Department of Abdominal Surgery, Aalborg University Hospital, Aalborg, Denmark.
Frank Svendsen
FS
Jensen
Department of Pathology, Aalborg University Hospital, Aalborg, Denmark.
Preben
P
Johansen
Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
Thomas
T
Urup
Department of Haematology, Aalborg University Hospital, Aalborg, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Tarec C
TC
El-Galaly
Department of Haematology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Jakob
J
Madsen
Department of Haematology, Aalborg University Hospital, Aalborg, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
Julie Støve
JS
Bødker
Department of Haematology, Aalborg University Hospital, Aalborg, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Karen
K
Dybkær
Department of Haematology, Aalborg University Hospital, Aalborg, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. Electronic address: haej@rn.dk.
Hans Erik
HE
Johnsen
D000368:Aged; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D018655:Lymphocyte Count; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D015398:Signal Transduction
D015415:Biomarkers