title: Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas.
abstract: Germinal centers (GCs) are sites of B-cell clonal expansion, hypermutation, and selection. GCs are polarized into dark (DZ) and light zones (LZ), a distinction that is of key importance to GC selection. However, the difference between the B cells in each of these zones in humans remains unclear. We show that, as in mice, CXCR4 and CD83 can be used to distinguish human LZ and DZ cells. Using these markers, we show that LZ and DZ cells in mice and humans differ only in the expression of characteristic "activation" and "proliferation" programs, suggesting that these populations represent alternating states of a single-cell type rather than distinct differentiation stages. In addition, LZ/DZ transcriptional profiling shows that, with the exception of "molecular" Burkitt lymphomas, nearly all human B-cell malignancies closely resemble LZ cells, which has important implications for our understanding of the molecular programs of lymphomagenesis.
authors: Laboratory of Molecular Immunology, Rockefeller University, New York, NY, USA. victora@wi.mit.edu
authors: Gabriel D
authors: GD
authors: Victora
authors: David
authors: D
authors: Dominguez-Sola
authors: Antony B
authors: AB
authors: Holmes
authors: Stephanie
authors: S
authors: Deroubaix
authors: Riccardo
authors: R
authors: Dalla-Favera
authors: Michel C
authors: MC
authors: Nussenzweig
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002051:Burkitt Lymphoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D014066:Palatine Tonsil / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D019718:Receptors, CXCR4; D000097802:CD83 Antigen