Phenotype and genotype of interfollicular large B cells, a subpopulation of lymphocytes often with dendritic morphology

Marafioti, Teresa; Jones, Margaret; Facchetti, Fabio; Diss, Tim C.; Du, Ming; Isaacson, Peter G.; Pozzobon, Michela; Pileri, Stefano; Strickson, Amanda J.; Tan, Soo-Yong; Watkins, Fiona; Mason, David Y.

doi:10.1182/blood-2003-03-0692

Cited by 92 publications

(99 citation statements)

References 70 publications

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“…1,10 Indeed, HCL and marginal zone B cells share several immunogenetic features, including variable tiers of IGHV mutations, evidence of ongoing somatic hypermutation and lack of novel N-glycosylation sites. 19,36,55 The morphology and phenotype of hairy cells also resemble those of marginal zone-derived CD23-negative, CD27-negative, CD38-negative interfollicular B cells. Overall, efforts should be directed at identifying the normal counterpart within these categories.…”

Section: Discussionmentioning

confidence: 91%

Selective influences in the expressed immunoglobulin heavy and light chain gene repertoire in hairy cell leukemia

Forconi¹,

Sozzi²,

Rossi³

et al. 2008

Haematologica

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Section: Discussionmentioning

confidence: 91%

Selective influences in the expressed immunoglobulin heavy and light chain gene repertoire in hairy cell leukemia

Forconi¹,

Sozzi²,

Rossi³

et al. 2008

Haematologica

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“…Lymph nodes also harbor a predominantly isotype-switched CD27 Àve pool of large inter-follicular B cells, but in marked contrast, these nodal B cells are extensively mutated. 16 It seems then that multiple pathways generate a repertoire of CD27 Àve memory B cells at different sites, with as yet unknown functions.…”

Section: Discussionmentioning

confidence: 99%

Defining origins of malignant B cells: a new circulating normal human IgM+D+ B-cell subset lacking CD27 expression and displaying somatically mutated IGHV genes as a relevant memory population

et al. 2009

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In probing the cell of origin in malignant B cells, an imprint of somatic hypermutation (SHM) in immunoglobulin (Ig) variable (V) region genes delineates antigen encounter, and identifying the precise pathway generating SHM in the normal B-cell counterpart becomes relevant. SHM remains the definitive memory imprint in normal human B cells, but CD27 expression also delineates memory. Recently, dye extrusion adenosine triphosphate-binding transporter assays identified circulating isotype-switched memory B cells that lacked CD27, yet exhibited low levels of SHM. To extend findings, we report a pre-switched CD27 Àve circulating memory B-cell population in normal blood using comparable assays, and isolated CD19 þ IgM þ D þ CD27 Àve cells (499% purity) for the analysis of IGHV5/IGHV3-IGHM transcripts. Of these (n ¼ 334), B78% were germ line and naive B cell derived. Strikingly, 21.9% of the transcripts were mutated. They showed 3-5 mutations (13.5% of sequences) and 45 mutations (8.4% of sequences) per transcript. Accrual of mutations in a subset of CD19 þ IgM þ D þ CD27 Àve cells define a new circulating pre-switched memory B-cell pool, present in substantial numbers in the population harboring naive B cells. These CD19 þ IgM þ D þ CD27 Àve memory B cells may have a distinct lineage and function, and seem relevant to understanding origins of malignant B cells, in particular those of hairy cell leukemia cells, which display mutated V genes yet lack CD27 expression.

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“…14,15 Briefly, slides were immunostained for MNDA by the two-stage peroxidase-based EnVision technique, washed in phosphate buffered saline (PBS) for up to 5 min, then incubated in normal human serum for up to 10 min before immunofluorescence labeling with Abs CD27 (red) and IgD (green) in normal spleen and reactive mesenteric lymph node (triple staining), and IgM (green) and CD20 (green) in normal spleen and reactive mesenteric lymph node (double staining). Immunofluorescence labeling was carried out as described previously.…”

Section: Immunoperoxidase Technique Combined With Immunofluorescencementioning

confidence: 99%

Identification of MNDA as a new marker for nodal marginal zone lymphoma

et al. 2009

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Clinical and biological studies on nodal marginal zone lymphoma (NMZL) are hampered by the lack of specific diagnostic markers and the low reproducibility of this diagnosis. A comparative expression-profiling study has shown a set of markers to be differentially expressed in NMZL compared with follicular lymphoma (FL), including myeloid cell nuclear differentiation antigen (MNDA), a nuclear protein expressed by myeloid cells and a subset of B-cells. The aim of this study was to characterize the expression of MNDA in normal and reactive human tissue, and in a large series of non-Hodgkin's B-cell lymphomas, with particular emphasis on NMZL and FL. Our results showed that MNDA is expressed in normal tissue by a subset of the marginal zone B cells. They also showed MNDA expression in subgroups of chronic lymphocytic leukemia, mantle-cell lymphoma, and diffuse large B-cell lymphoma, but MNDA was especially expressed by lymphomas derived from the marginal zone, such as mucosa-associated lymphoid-tissue lymphoma, splenic marginal-zone lymphoma and NMZL. MNDA expression was rarely observed in FL, a characteristic that is of potential value in distinguishing between NMZL and FL. MNDA expression is thus a useful tool for the recognition of NMZL.

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Phenotype and genotype of interfollicular large B cells, a subpopulation of lymphocytes often with dendritic morphology

Cited by 92 publications

References 70 publications

Selective influences in the expressed immunoglobulin heavy and light chain gene repertoire in hairy cell leukemia

Selective influences in the expressed immunoglobulin heavy and light chain gene repertoire in hairy cell leukemia

Defining origins of malignant B cells: a new circulating normal human IgM+D+ B-cell subset lacking CD27 expression and displaying somatically mutated IGHV genes as a relevant memory population

Identification of MNDA as a new marker for nodal marginal zone lymphoma

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