The Germinal centre‐derived lymphomas seen through their cellular microenvironment

Carbone, Antonino; Gloghini, Annunziata; Cabras, Antonello D.; Elia, Giuliano

doi:10.1111/j.1365-2141.2009.07651.x

Cited by 46 publications

(47 citation statements)

References 84 publications

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“…Furthermore, nodules of this form of lymphoma are characterized by an increase of germinal center-derived CD57 + T cells which are closely associated with neoplastic lymphocyte-predominant cells. 19 These CD57 + T cells also express markers reminiscent of germinal center TH cells such as PD1, BCL6, IRF4/MUM1 and c-MAF. 19 Altogether these data suggest that some of these reactive cells could be TFH cells, but a more precise micro-dissection of the microenvironment is required to confirm this.…”

Section: Implications Of Follicular T-helper Cells In Lymphomamentioning

confidence: 99%

“…19 In order to proliferate, follicular lymphoma cells require cellular interactions such as those in normal germinal centers, including contacts with germinal center TH cells which express CD3, CD4, CD57, PD1 and CXCL13. 19 Proliferation is stimulated by CD40-CD40L interaction, markers expressed on malignant B cells and TFH cells, respectively. 19 This is further supported by the presence of significant amounts of PD1 in the germinal centers of patients with follicular lymphoma, as shown in a recent study.…”

Section: Implications Of Follicular T-helper Cells In Lymphomamentioning

confidence: 99%

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A novel subset of T-helper cells: follicular T-helper cells and their markers

Laurent¹,

Fazilleau²,

Brousset³

2010

Haematologica

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ML, et al. Mutations in the genes coding for the NF-{kappa}B regulating factors IκBα and A20 are uncommon in nodular lymphocyte-predominant Hodgkin lymphoma. Haematologica. 2010; 95(1) 1 TFH cells are characterized by their homing capacity in CXCL13-rich areas, such as B-cell follicles, through CXCR5 expression and their ability to support immunoglobulin production. The differentiation and homing of TFH, as well as their interactions with B cells, have been the subject of intense research and several markers have been identified as components of the TFH signature. Thanks to gene expression profiling carried out on peripheral T-cell lymphomas, a TFH signature has been reported in angioimmunoblastic T-cell lymphoma (AITL) and in follicular T-cell lymphoma.2-4 Several markers that identify TFH cells are now used in hematopathology to reinforce the diagnostic criteria of AITL. In this issue of the Journal, Marafioti et al.5 describe that inducible T-cell co-stimulatory molecule (ICOS), a CD28 homolog implicated in the regulation of T-cell differentiation and function, appears to be a relevant marker for the diagnosis of TFH-derived lymphoma such as AITL and follicular T-cell lymphoma. This review first summarizes the recent evidence on TFH cell differentiation and the present state of knowledge on molecules expressed by TFH cells. Then, from this perspective, the potential implications of TFH cells in lymphomagenesis and as part of the tumor microenvironment are covered. Lineage and differentiation of follicular T-helper cellsTH cell responses are heterogeneous and effector function choice is imposed during initial activation of the naïve TH cells through the expression of transcription factors. It is now clear that TFH cells belong to a subset of TH cells that differ from the other TH cell subsets. Indeed, TH1 cells express STAT4, STAT1 and T-box transcription factor/Tbet, TH2 cells express GATA3, TH17 cells express retinoid related orphan receptor (RORγt) and regulatory T cells (Treg) express FOXP3. It has recently been shown that the TFH cell differentiation program is controlled by BCL6. 6,7 TFH cells upregulate BCL6 which in turn blocks TH1, TH2 and TH17 cell differentiation by repressing their selective transcription factors. 6 Moreover, BCL6 antagonizes the expression of Blimp-1 transcription factor, which is preferentially expressed by TH cells in the T zone area. 6,8 BCL6 also represses the expression of miR-17-92, a micro RNA that down-regulates CXCR5 expression, which is essential for TFH cell function. Finally over-expression of BCL6 in activated TH cells induces expression of interleukin (IL)-6 receptor and IL-21 receptor, which are both required for TFH cell generation as shown by the role of IL-6 and IL-21 in TFH cell differentiation.9 ICOS is also implicated in the regulation of TFH cell differentiation. Once engaged with its ligand (ICOS-L), expressed on antigen-presenting cells including B cells, ICOS induces the production of helper cytokines such as IL-2, IL-4 and especially IL-10 and IL-21.10 I...

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Section: Implications Of Follicular T-helper Cells In Lymphomamentioning

confidence: 99%

Section: Implications Of Follicular T-helper Cells In Lymphomamentioning

confidence: 99%

A novel subset of T-helper cells: follicular T-helper cells and their markers

Laurent¹,

Fazilleau²,

Brousset³

2010

Haematologica

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“…NLPHL has distinctive morphologic, immunophenotypic, and molecular features that distinguish it from classical Hodgkin lymphoma. Although FDCs have not been implicated in the pathogenesis of NLPHL, the popcorn cells usually reside in nodules that have variably distorted and disintegrated FDC meshworks [59,60]. Most T cells within the nodules of NLPHL are germinal center-derived CD4, CD57, and PD-1 positive T cells that form rings or rosettes surrounding the popcorn cells.…”

Section: Fdcs In Nodular Lymphocyte Predominant Hodgkin Lymphomamentioning

confidence: 99%

Follicular dendritic cells: origin, function, and different disease-associated patterns

et al. 2013

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Summary Follicular dendritic cells (FDCs) are a specialized type of antigen-presenting dendritic cells that are largely restricted to lymphoid follicles. They form dense three-dimensional meshwork patterns within benign follicles, which maintain the follicular architecture. The FDC function is to bind and retain antigens by linking to complement and immune complexes and then present these antigens to germinal center B cells that start the secondary immune response. FDCs aid in the rescue of bound B cells from apoptosis, and induce the differentiation of B cells into long-term memory B cell clones or plasma cells. We will discuss the different patterns of the FDC meshwork observed in different types of reactive and neoplastic disorders, which may be due to underlying different roles that FDCs may play in these disorders and whether changes in the architecture of the FDC meshwork can be useful in routine diagnostic practice or have a prognostic value.

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“…Besides ''in situ'' FL, an intrafollicular neoplasia may be observed in other lymphomas in which the putative normal counterpart of the tumor cell is located in the GC or the mantle zone or the marginal zone of the follicle [7]. These lymphomas include nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) [8], angioimmunoblastic T-cell lymphoma (AITL) showing limited paracortical involvement [9,10], mantle cell lymphoma (MCL) [11], and cases of nodal marginal zone lymphoma [12] (see Fig.…”

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confidence: 99%