Regulation of CCR6 chemokine receptor expression and responsiveness to macrophage inflammatory protein-3α/CCL20 in human B cells

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2338-2345 ◽  
Author(s):  
Roman Krzysiek ◽  
Eric A. Lefevre ◽  
Jérôme Bernard ◽  
Arnaud Foussat ◽  
Pierre Galanaud ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Chemokine Receptor ◽  
Memory B Cells ◽  
Receptor Expression ◽  
B Cell Differentiation ◽  
Hematopoietic Stem ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein

The regulation of CCR6 (chemokine receptor 6) expression during B-cell ontogeny and antigen-driven B-cell differentiation was analyzed. None of the CD34+Lin− hematopoietic stem cell progenitors or the CD34+CD19+ (pro-B) or the CD19+CD10+ (pre-B/immature B cells) B-cell progenitors expressed CCR6. CCR6 is acquired when CD10 is lost and B-cell progeny matures, entering into the surface immunoglobulin D+ (sIgD+) mature B-cell pool. CCR6 is expressed by all bone marrow–, umbilical cord blood–, and peripheral blood–derived naive and/or memory B cells but is absent from germinal center (GC) B cells of secondary lymphoid organs. CCR6 is down-regulated after B-cell antigen receptor triggering and remains absent during differentiation into immunoglobulin-secreting plasma cells, whereas it is reacquired at the stage of post-GC memory B cells. Thus, within the B-cell compartment, CCR6 expression is restricted to functionally mature cells capable of responding to antigen challenge. In transmigration chemotactic assays, macrophage inflammatory protein (MIP)-3α/CC chemokine ligand 20 (CCL20) induced vigorous migration of B cells with differential chemotactic preference toward sIgD− memory B cells. These data suggest that restricted patterns of CCR6 expression and MIP-3α/CCL20 responsiveness are integral parts of the process of B-lineage maturation and antigen-driven B-cell differentiation.

Regulation of CCR6 chemokine receptor expression and responsiveness to macrophage inflammatory protein-3α/CCL20 in human B cells

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2338-2345 ◽  
Author(s):  
Roman Krzysiek ◽  
Eric A. Lefevre ◽  
Jérôme Bernard ◽  
Arnaud Foussat ◽  
Pierre Galanaud ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Chemokine Receptor ◽  
Memory B Cells ◽  
Receptor Expression ◽  
B Cell Differentiation ◽  
Hematopoietic Stem ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein

Abstract The regulation of CCR6 (chemokine receptor 6) expression during B-cell ontogeny and antigen-driven B-cell differentiation was analyzed. None of the CD34+Lin− hematopoietic stem cell progenitors or the CD34+CD19+ (pro-B) or the CD19+CD10+ (pre-B/immature B cells) B-cell progenitors expressed CCR6. CCR6 is acquired when CD10 is lost and B-cell progeny matures, entering into the surface immunoglobulin D+ (sIgD+) mature B-cell pool. CCR6 is expressed by all bone marrow–, umbilical cord blood–, and peripheral blood–derived naive and/or memory B cells but is absent from germinal center (GC) B cells of secondary lymphoid organs. CCR6 is down-regulated after B-cell antigen receptor triggering and remains absent during differentiation into immunoglobulin-secreting plasma cells, whereas it is reacquired at the stage of post-GC memory B cells. Thus, within the B-cell compartment, CCR6 expression is restricted to functionally mature cells capable of responding to antigen challenge. In transmigration chemotactic assays, macrophage inflammatory protein (MIP)-3α/CC chemokine ligand 20 (CCL20) induced vigorous migration of B cells with differential chemotactic preference toward sIgD− memory B cells. These data suggest that restricted patterns of CCR6 expression and MIP-3α/CCL20 responsiveness are integral parts of the process of B-lineage maturation and antigen-driven B-cell differentiation.

scholarly journals THU0043 EXPRESSION OF B CELL CHEMOKINE-CHEMOKINE RECEPTOR PATHWAYS IS ALTERED IN GIANT CELL ARTERITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 234.2-234
Author(s):  
J. Graver ◽  
A. Boots ◽  
W. Abdulahad ◽  
J. Bijzet ◽  
D. Wolbers ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Chemokine Receptor ◽  
Temporal Artery ◽  
Absolute Number ◽  
Memory B Cells ◽  
Receptor Expression ◽  
Healthy Controls ◽  
B Cell Differentiation

Background:The presence of organised B cells in both cranial-giant cell arteritis (C-GCA) (temporal artery) and large vessel (LV)-GCA (aorta) has previously been documented. The number and the extent of organisation of B cells in tertiary lymphoid organs (TLO) was more prominent in the aorta than in the temporal artery, suggesting possible differences in B cell phenotype, kinetics and tropism between C-GCA and LV-GCA.Objectives:We sought to analyse B cell differentiation subsets in both C-GCA and LV-GCA and to investigate differences in the expression of chemokine pathways involved in B cell migration and TLO organisation.Methods:Blood was collected from C-GCA (n=11) and LV-GCA (n=22) patients at baseline, before start of glucocorticoid treatment, and after 3 months of treatment. The LV-GCA groups consisted of 11 patients with isolated LV-GCA and 11 patients with overlap LV/C-GCA. Also, age- and sex- matched healthy controls (HC, n=24) were included. The following chemokines were measured with Luminex in the sera of patients and HC: BAFF, CCL19, CCL21, CXCL9, CXCL10, CXCL11, CXCL12, and CXCL13. Thawed PBMC of 7 C-GCA, 10 LV-GCA and 24 HC were stained with antibodies against CD19, CD27, IgD, IgM, CD38, CXCR3, CXCR4, CXCR5, and CCR7 to allow identification of B cell differentiation subsets and their chemokine receptor expression.Results:We found a lower absolute number of CXCR3+ memory and double negative (late stage) B cells in GCA patients when compared to healthy controls. Also, the absolute number of CXCR5+ memory B cells was lower in patients than in controls. Chemokine receptor expression on circulating B cells did not significantly differ between C-GCA and LV-GCA at baseline. After 3 months of treatment, frequencies and absolute numbers of both CXCR3+ and CXCR5+ memory B cells increased. In sera of all GCA patients, CXCL9 (which is a chemokine involved in migration of B cells to sites of inflammation) and CXCL13 (which is involved in local organization of B cells) were significantly increased. BAFF and CCL21 were increased only in LV-GCA when compared to HC. Serum chemokine levels did not differ between C-GCA and LV-GCA patients. An inverse correlation was observed between B cell counts and CXCL9 as well as CXCL13 in LV-GCA, only. After 3 months of treatment, CXCL9 levels remained elevated whereas CXCL13 increased even further.Conclusion:At diagnosis, CXCL9 and CXCL13 were significantly increased in all GCA patients as compared to HC. Elevated CXCL9 levels inversely correlated with B cells numbers in LV-GCA, only, which may suggest that B cells preferentially migrate to the inflamed aorta via a mechanism involving CXCL9. In addition, CXCL13 may be linked to local TLO organization in LV-GCA. Currently, we are studying the local expression of chemokines and chemokine receptors at the site of inflammation in both C- and LV-GCA.Disclosure of Interests:Jacoba Graver: None declared, Annemieke Boots Consultant of: Grünenthal Gmbh until 2017, Wayel Abdulahad: None declared, Johan Bijzet: None declared, Daphne Wolbers: None declared, Elisabeth Brouwer Consultant of: Roche (consultancy fee 2017 and 2018 paid to the UMCG), Speakers bureau: Roche (2017 and 2018 paid to the UMCG), Maria Sandovici: None declared

Interleukin-5 (IL-5) and IL-6 define two molecularly distinct pathways of B-cell differentiation

1993 ◽  
Vol 13 (7) ◽  
pp. 3929-3936
Author(s):  
T D Randall ◽  
F E Lund ◽  
J W Brewer ◽  
C Aldridge ◽  
R Wall ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
B Cell Lymphoma ◽  
Receptor Expression ◽  
High Rate ◽  
B Cell Differentiation ◽  
Interleukin 5 ◽  
Stage Of Development ◽  
Differentiation Factors

Interleukin-5 (IL-5) and IL-6 have both been reported to act as B-cell differentiation factors by stimulating activated B cells to secrete antibody. However, it has not been possible to directly compare the effects of these two lymphokines because of the lack of a suitable B-cell line capable of responding to both. We have identified a clonal, inducible B-cell lymphoma, CH12, that has this property. Both IL-5 and IL-6 can independently stimulate increases in steady-state levels of immunoglobulin and J-chain mRNA and proteins, and they both induce the differentiation of CH12 into high-rate antibody-secreting cells. Nevertheless, there are significant differences in the activities of these two lymphokines. First, while IL-6 acts only as a differentiation factor, IL-5 also augments the proliferation of CH12 cells. Second, the differentiation stimulated by IL-5 but not by IL-6 is partially inhibited by IL-4. Inhibition of IL-5-induced differentiation was not at the level of IL-5 receptor expression, since IL-4 did not inhibit IL-5-induced proliferation. Third, IL-5 but not IL-6 stimulated increased mouse mammary tumor proviral gene expression in CH12 cells. These results demonstrate that while both IL-5 and IL-6 may act as differentiation factors for B cells, they induce differentiation by using at least partially distinct molecular pathways. Our results also establish that B cells characteristic of a single stage of development can independently respond to IL-4, IL-5, and IL-6.

scholarly journals Interleukin-5 (IL-5) and IL-6 define two molecularly distinct pathways of B-cell differentiation.

1993 ◽  
Vol 13 (7) ◽  
pp. 3929-3936 ◽  
Author(s):  
T D Randall ◽  
F E Lund ◽  
J W Brewer ◽  
C Aldridge ◽  
R Wall ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
B Cell Lymphoma ◽  
Receptor Expression ◽  
High Rate ◽  
B Cell Differentiation ◽  
Interleukin 5 ◽  
Stage Of Development ◽  
Differentiation Factors

Interleukin-5 (IL-5) and IL-6 have both been reported to act as B-cell differentiation factors by stimulating activated B cells to secrete antibody. However, it has not been possible to directly compare the effects of these two lymphokines because of the lack of a suitable B-cell line capable of responding to both. We have identified a clonal, inducible B-cell lymphoma, CH12, that has this property. Both IL-5 and IL-6 can independently stimulate increases in steady-state levels of immunoglobulin and J-chain mRNA and proteins, and they both induce the differentiation of CH12 into high-rate antibody-secreting cells. Nevertheless, there are significant differences in the activities of these two lymphokines. First, while IL-6 acts only as a differentiation factor, IL-5 also augments the proliferation of CH12 cells. Second, the differentiation stimulated by IL-5 but not by IL-6 is partially inhibited by IL-4. Inhibition of IL-5-induced differentiation was not at the level of IL-5 receptor expression, since IL-4 did not inhibit IL-5-induced proliferation. Third, IL-5 but not IL-6 stimulated increased mouse mammary tumor proviral gene expression in CH12 cells. These results demonstrate that while both IL-5 and IL-6 may act as differentiation factors for B cells, they induce differentiation by using at least partially distinct molecular pathways. Our results also establish that B cells characteristic of a single stage of development can independently respond to IL-4, IL-5, and IL-6.

scholarly journals Favorable efficacy of rituximab in ANCA-associated vasculitis patients with excessive B cell differentiation

2020 ◽  
Author(s):  
Yusuke Miyazaki ◽  
Shingo Nakayamada ◽  
Satoshi Kubo ◽  
Yuichi Ishikawa ◽  
Maiko Yoshikawa ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Selection Criteria ◽  
Memory B Cells ◽  
Phenotypic Characterization ◽  
B Cell Differentiation ◽  
Color Flow ◽  
Anca Associated Vasculitis ◽  
Cell Phenotypes

Abstract Objectives: B-cell depletion by rituximab (RTX) is an effective treatment for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). However, peripheral B cell phenotypes and the selection criteria for RTX therapy in AAV remain unclear.Methods: Phenotypic characterization of circulating B cells was performed by 8-color flow cytometric analysis in 54 newly diagnosed AAV patients (20 granulomatosis with polyangiitis and 34 microscopic polyangiitis). Patients were considered eligible to receive intravenous cyclophosphamide pulse (IV-CY) or RTX. All patients also received high-dose glucocorticoids (GC). We assessed circulating B cell phenotypes and evaluated the efficacy after 6 months of treatment. Results: There were no significant differences in the rate of clinical improvement, relapses, or serious adverse events between patients receiving RTX and IV-CY. The rate of Birmingham Vasculitis Activity Score (BVAS)-improvement at 6 months tended to be higher in the RTX group than in the IV-CY group. The proportion of effector or class-switched memory B cells increased in 24 out of 54 patients (44%). The proportions of peripheral T and B cell phenotypes did not correlate with BVAS at baseline. However, among peripheral B cells, the proportion of class-switched memory B cells negatively correlated with the rate of improvement in BVAS at 6 months after treatment initiation (r = -0.28, p = 0.04). Patients with excessive B cell differentiation were defined as those in whom the proportion of class-switched memory B cells or IgD-CD27- B cells among all B cells was >2 SDs higher than the mean in the HCs. The rate of BVAS-remission in patients with excessive B cell differentiation was significantly lower than that in patients without. In patients with excessive B cell differentiation, the survival rate, the rate of BVAS-remission, and dose reduction of GC were significantly improved in the RTX group compared to those in the IV-CY group after 6 months of treatment. Conclusions: The presence of excessive B cell differentiation was associated with treatment resistance. However, in patients with circulating B cell abnormality, RTX was effective and increased survival compared to IV-CY. The results suggest that multi-color flow cytometry may be useful to determine the selection criteria for RTX therapy in AAV patients. (349/350 words)

scholarly journals Distinct pathways regulated by menin and by MLL1 in hematopoietic stem cells and developing B cells

Blood ◽  
2013 ◽  
Vol 122 (12) ◽  
pp. 2039-2046 ◽  
Author(s):  
Bin E. Li ◽  
Tao Gan ◽  
Matthew Meyerson ◽  
Terence H. Rabbitts ◽  
Patricia Ernst
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
B Cells ◽  
Hematopoietic Stem Cells ◽  
B Cell ◽  
Hematopoietic Stem Cell ◽  
B Cell Differentiation ◽  
Hematopoietic Stem ◽  
Key Points

Key Points MLL1 does not require interaction with menin to maintain hematopoietic stem cell homeostasis. Menin and MLL1 are both critical during B-cell differentiation, but largely through distinct pathways.

Expression of macrophage inflammatory protein-3α, stromal cell–derived factor-1, and B-cell–attracting chemokine-1 identifies the tonsil crypt as an attractive site for B cells

Blood ◽  
2001 ◽  
Vol 97 (12) ◽  
pp. 3992-3994 ◽  
Author(s):  
Montserrat Casamayor-Pallejà ◽  
Paul Mondière ◽  
Ali Amara ◽  
Chantal Bella ◽  
Marie-Caroline Dieu-Nosjean ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Stromal Cell ◽  
Plasma Cells ◽  
Close Contact ◽  
Memory B Cells ◽  
Inflammatory Protein ◽  
Stromal Cell Derived Factor ◽  
With Memory ◽  
Macrophage Inflammatory Protein

The expression of 3 lymphoid chemokines—macrophage inflammatory protein-3α (MIP-3α), stromal cell–derived factor-1 (SDF-1), and B-cell–attracting chemokine-1 (BCA-1)—in the tonsil and the possible correlation between their sites of expression and B-cell localization within this tissue were studied. The results show that all 3 chemokines are produced in the crypts but differ by the nature of the cells that produce them and their location within the crypt. SDF-1 and MIP-3α are produced by epithelial cells, but their secretion is mutually exclusive. Both MIP-3α– and SDF-1–expressing cells are in close contact with memory B cells. By contrast, BCA-1–producing cells in the crypt are not epithelial and form clusters colocalized with plasma cells. Altogether, these data suggest that the chemokines produced in the tonsillar crypt may (1) attract memory B cells to antigen and (2) recruit and retain plasma cells and memory B cells within the supportive epithelial microenvironment of the crypt.

scholarly journals IL-21 regulates germinal center B cell differentiation and proliferation through a B cell–intrinsic mechanism

2010 ◽  
Vol 207 (2) ◽  
pp. 365-378 ◽  
Author(s):  
Dimitra Zotos ◽  
Jonathan M. Coquet ◽  
Yang Zhang ◽  
Amanda Light ◽  
Kathy D'Costa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Affinity Maturation ◽  
Memory B Cells ◽  
Target Cells ◽  
B Cell Differentiation ◽  
Follicular Helper

Germinal centers (GCs) are sites of B cell proliferation, somatic hypermutation, and selection of variants with improved affinity for antigen. Long-lived memory B cells and plasma cells are also generated in GCs, although how B cell differentiation in GCs is regulated is unclear. IL-21, secreted by T follicular helper cells, is important for adaptive immune responses, although there are conflicting reports on its target cells and mode of action in vivo. We show that the absence of IL-21 signaling profoundly affects the B cell response to protein antigen, reducing splenic and bone marrow plasma cell formation and GC persistence and function, influencing their proliferation, transition into memory B cells, and affinity maturation. Using bone marrow chimeras, we show that these activities are primarily a result of CD3-expressing cells producing IL-21 that acts directly on B cells. Molecularly, IL-21 maintains expression of Bcl-6 in GC B cells. The absence of IL-21 or IL-21 receptor does not abrogate the appearance of T cells in GCs or the appearance of CD4 T cells with a follicular helper phenotype. IL-21 thus controls fate choices of GC B cells directly.

scholarly journals Favorable efficacy of rituximab in ANCA-associated vasculitis patients with excessive B cell differentiation

2020 ◽  
Author(s):  
Yusuke Miyazaki ◽  
Shingo Nakayamada ◽  
Satoshi Kubo ◽  
Yuichi Ishikawa ◽  
Maiko Yoshikawa ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Selection Criteria ◽  
Memory B Cells ◽  
Phenotypic Characterization ◽  
B Cell Differentiation ◽  
Color Flow ◽  
Anca Associated Vasculitis ◽  
Cell Phenotypes

Abstract Objectives: B-cell depletion by rituximab (RTX) is an effective treatment for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). However, peripheral B cell phenotypes and the selection criteria for RTX therapy in AAV remain unclear.Methods: Phenotypic characterization of circulating B cells was performed by 8-color flow cytometric analysis in 54 newly diagnosed AAV patients (20 granulomatosis with polyangiitis and 34 microscopic polyangiitis). Patients were considered eligible to receive intravenous cyclophosphamide pulse (IV-CY) or RTX. All patients also received high-dose glucocorticoids (GC). We assessed circulating B cell phenotypes and evaluated the efficacy after 6 months of treatment. Results: There were no significant differences in the rate of clinical improvement, relapses, or serious adverse events between patients receiving RTX and IV-CY. The proportion of effector or class-switched memory B cells increased in 24 out of 54 patients (44%). The proportions of peripheral T and B cell phenotypes did not correlate with BVAS at baseline. However, among peripheral B cells, the proportion of class-switched memory B cells negatively correlated with the rate of improvement in BVAS at 6 months after treatment initiation (r = -0.28, p = 0.04). Patients with excessive B cell differentiation were defined as those in whom the proportion of class-switched memory B cells or IgD-CD- B cells among all B cells was >2 SDs higher than the mean in the HCs. The rate of Birmingham Vasculitis Activity Score (BVAS) remission in patients with excessive B cell differentiation was significantly lower than that in patients without. In patients with excessive B cell differentiation, the survival rate, the rate of BVAS remission, and dose reduction of GC were significantly improved in the RTX group compared to those in the IV-CY group after 6 months of treatment. Conclusions: The presence of excessive B cell differentiation was associated with treatment resistance. However, in patients with circulating B cell abnormality, RTX was effective and increased survival compared to IV-CY. The results suggest that multi-color flow cytometry may be useful to determine the selection criteria for RTX therapy in AAV patients.

Differentiation-Stage-Specific Expression of MicroRNAs in B-Lymphocytes and Diffuse Large B-Cell Lymphomas (DLBCL)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 805-805 ◽  
Author(s):  
Raquel Malumbres ◽  
Robert Tibshirani ◽  
Elena Cubedo ◽  
Kristopher A Sarosiek ◽  
Xiaoyu Jiang ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Memory B Cells ◽  
Microrna Expression ◽  
B Cell Differentiation ◽  
Cell Of Origin ◽  
Specific Expression ◽  
Differentiation Stage

Abstract B-cell development and differentiation are complex processes controlled by distinct programs of transcriptional control. A large set of transcriptional factors together or in succession control this process and their deregulation may result in block of differentiation or malignant transformation. MicroRNAs are small RNAs that orchestrate cellular functions by modulating the level of their targeted proteins by either translational arrest or transcript degradation, and play a key role in cell differentiation, apoptosis, proliferation and cancer development. An increasing number of transcription factors are being found targeted by microRNAs. Emerging evidence suggests that differentiation stage-specific expression of microRNAs occurs in the hematopoietic system and during T cell differentiation. Only limited information exists on microRNA expression in normal B cell differentiation and its malignant counterparts. Herein we analyzed microRNA expression profiles in distinct peripheral B cell differentiation stages-naïve, germinal center (GC) centroblasts and memory cells as well as tonsilar T cells. Furthermore, microRNA profiling was performed in germinal center-like (GCB-like) and activated B-cell-like (ABC-like) DLBCL cell lines originating from distinct B-cell differentiation stages. RNA, extracted with mirVana kit (AMBION) from B cell subsets and T cells enriched from normal tonsils was hybridized on LC Sciences (Houston, TX) microarrays harboring 470 human microRNAs probes (Sanger miRBase Release 9.1). Expression of selected microRNAs was confirmed by ABI RT-PCR methodology. Unsupervised clustering of microRNAs with values present in at least 50% of the samples (122 probes) resulted in perfect differentiation-stage clustering of samples. Application of Statistical Analysis of Microarrays (SAM) and Prediction Analysis of Microarrays (PAM) methods (FDR= 10%) identified a 47 microRNA cell of origin classifier for B-cells differentiation stage; 27 of these microRNAs were upregulated and 20 downregulated in centroblasts compared to memory B-cells. MicroRNAs belonging to paralog microRNA clusters (e.g. miR17-92-1, miR363-106a and miR25-106b) demonstrated similar patterns of expression in specific differentiation stages. To identify specific microRNA targets, miRanda, TargetScan and PicTar programs were used. To experimentally confirm the targets, we assessed the effects of specific microRNAs on the expression levels of targeted proteins and on the luciferase reporter under the control of the wild type and mutated 3′ UTR regions of putative target genes. Using this experimental approach we identified lymphocyte-stage-specific microRNAs which expression inversely correlated and might regulate the expression of LMO2, BLIMP1 and IRF4 proteins distinctively expressed at different differentiation stages of B lymphocytes. For example, miR223, which expression is low in GC cells but is high in naïve and memory B cells, downregulates the expression of LMO2. We next analyzed microRNA expression in DLBCL cell lines. Clustering analysis, using the 47 microRNA cell of origin classifier perfectly classified GCB-like and ABC-like cell lines. Interestingly, the expression of microRNAs in both GCB-like and ABC-like DLBCL cell lines was more similar to normal centroblasts than to memory B cells, suggesting that both may originate from distinct subpopulations of GC lymphocytes. The similarity of microRNA expression in cell lines to centroblasts was striking, with only 16 microRNAs (1 upregulated and 15 downregulated in cell lines) showing noticeable differences in levels of expression compared to normal cells. These microRNAs might be involved in the process of lymphoma transformation. SAM analysis aimed to differentiate GCB-like and ABC-like cell lines identified 11 microRNAs, only 3 of which were present in the cell of origin classifier. This observation suggests that there is also a difference in expression of microRNAs not directly related to the distinct cell of origin between the DLBCL subtypes. In summary, our results demonstrate that the microRNA profile changes during the GC reaction as well as during malignant transformation. Specific microRNAs can regulate key transcription factors controlling the processes of lymphocyte differentiation and transformation.

Sign in / Sign up

Export Citation Format

Share Document