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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.

SUBMITTER: Victora GD 

PROVIDER: S-EPMC3447782 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas.

Victora Gabriel D GD   Dominguez-Sola David D   Holmes Antony B AB   Deroubaix Stephanie S   Dalla-Favera Riccardo R   Nussenzweig Michel C MC  

Blood 20120626 11


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 characteri  ...[more]

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