Characterization of memory B cells from thymus and its impact for DLBCL classification

• Published in: Experimental hematology 2016-10, Vol.44 (10), p.982-990.e11
• Main Authors: Bergkvist, Kim Steve, Nørgaard, Martin Agge, Bøgsted, Martin, Schmitz, Alexander, Nyegaard, Mette, Gaihede, Michael, Bæch, John, Grønholdt, Marie-Louise, Jensen, Frank Svendsen, Johansen, Preben, Urup, Thomas, El-Galaly, Tarec C, Madsen, Jakob, Bødker, Julie Støve, Dybkær, Karen, Johnsen, Hans Erik
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Aged; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; B-Lymphocyte Subsets - pathology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Biomarkers; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Hematology, Oncology and Palliative Medicine; Humans; Immunologic Memory; Immunophenotyping; Lymphocyte Count; Lymphoma, Large B-Cell, Diffuse - diagnosis; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - immunology; Lymphoma, Large B-Cell, Diffuse - metabolism; Male; Middle Aged; Organ Specificity - genetics; Phenotype; Signal Transduction
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2016.06.001

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.