scholarly journals Increased Production of B-Cell Activating Cytokines and Altered Peripheral B-Cell Subset Distribution during HIV-Related Classical Hodgkin Lymphoma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 128
Author(s):  
Raphael Lievin ◽  
Houria Hendel-Chavez ◽  
Aliou Baldé ◽  
Rémi Lancar ◽  
Michèle Algarte-Génin ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cell Activation ◽  
Cell Subset ◽  
Serum Levels ◽  
Classical Hodgkin Lymphoma ◽  
Cell Counts ◽  
Cytokine Levels ◽  
B Cell Subsets

Classical Hodgkin Lymphoma incidence increases in HIV-1-infected patients (HIV-cHL). HIV infection is associated with higher B-cell activation. Here, in 38 HIV-cHL patients from the French cohort ANRS-CO16 Lymphovir, we examined longitudinally over 24 months the serum levels of the B-cell activating cytokines IL10, IL6, and BAFF, and blood distribution of B-cell subsets. Fourteen HIV-cHL patients were also compared to matched HIV-infected controls without cHL. IL10, IL6, and BAFF levels were higher in HIV-cHL patients than in controls (p < 0.0001, p = 0.002, and p < 0.0001, respectively). Cytokine levels increased in patients with advanced-stage lymphoma compared to those with limited-stage (p = 0.002, p = 0.03, and p = 0.01, respectively). Cytokine levels significantly decreased following HIV-cHL diagnosis and treatment. Blood counts of whole B-cells were similar in HIV-cHL patients and controls, but the distribution of B-cell subsets was different with higher ratios of naive B-cells over memory B-cells in HIV-cHL patients. Blood accumulation of naive B-cells was more marked in patients with advanced cHL stages (p = 0.06). During the follow-up, total B-cell counts increased (p < 0.0001), and the proportion of naive B-cells increased further (p = 0.04). Together the results suggest that in HIV-infected patients, cHL is associated with a particular B-cell-related environment that includes increased production of B-cell-activating cytokines and altered peripheral distribution of B-cell subsets. This B-cell-related environment may fuel the process of tumorigenesis.

scholarly journals Carrier-directed anti-hapten responses by b-cell subsets

1977 ◽  
Vol 146 (1) ◽  
pp. 1-10 ◽  
Author(s):  
GK Lewis ◽  
JW Goodman
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Burst Size ◽  
Cell Subset ◽  
B Cell Activation ◽  
Cell Subpopulations ◽  
Activation Pathways ◽  
B Cell Subsets

The capacity of the trinitrophenyl (TNP) haptenic group, coupled to a series of chemically dissimilar carriers, to cross-stimulate putative T- dependent and T-independent murine B-cell subpepulations was determined by using an in vitro limiting dilution technique to generate primary IgM responses. It was found that TNP-Ficoll and TNP-dextran, two T- independent antigens with little or no polyclonal mitogenicity, stimulate the same population of anti-TNP precursors, which is distinct from the precursor population activated by TNP-bacterial lipopolysaccharide (LPS), a T-independent polyclonal mitogen, or TNP-horse erythrocytes (HRBC), a T-dependent antigen. On the other hand, TNP-LPS and TNP-HRBC activate the same precursor population, indicating that LPS can substitute for the T- cell signal in T-dependent B-cell responses, whereas nonmitogenic T- independent antigens cannot. However, the cumulative evidence from this and other laboratories strongly indicates that LPS and T-dependent antigens activate B cells by different mechanisms. Of particular interest, LPS is incapable of activating B cells responsive to weakly- or nonmitogenic T-independent antigens. Based on clonal burst size, T-dependent antigens are capable of inducing greater antigen-specific B-cell proliferation than T-independent antigens. However, TNP conjugates of Ficoll and dextran, which are relatively poor inducers of polyclonal B-cell activation, induced larger anti-TNP clones than did TNP-LPS, a strong polyclonal mitogen. The findings reinforce the evidence favoring existence of multiple B- cell subpopulations with distinctive activation pathways. They also strengthen the proposition that a given B-cell subset can be activated by more than one mechanism.

scholarly journals Beyond Macrophages and T Cells: B Cells and Immunoglobulins Determine the Fate of the Atherosclerotic Plaque

2020 ◽  
Vol 21 (11) ◽  
pp. 4082 ◽  
Author(s):  
Harald Mangge ◽  
Florian Prüller ◽  
Wolfgang Schnedl ◽  
Wilfried Renner ◽  
Gunter Almer
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Cell Subset ◽  
Concomitant Disease ◽  
Metabolic Dysfunction ◽  
Clinical Endpoints ◽  
B Cell Subsets

Atherosclerosis (AS) leading to myocardial infarction and stroke remains worldwide the main cause for mortality. Vulnerable atherosclerotic plaques are responsible for these life-threatening clinical endpoints. Atherosclerosis is a chronic, complex, inflammatory disease with interactions between metabolic dysfunction, dyslipidemia, disturbed microbiome, infectious triggers, vascular, and immune cells. Undoubtedly, the immune response is a most important piece of the pathological puzzle in AS. Although macrophages and T cells have been the focus of research in recent years, B cells producing antibodies and regulating T and natural killer (NKT) cell activation are more important than formerly thought. New results show that the B cells exert a prominent role with atherogenic and protective facets mediated by distinct B cell subsets and different immunoglobulin effects. These new insights come, amongst others, from observations of the effects of innovative B cell targeted therapies in autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). These diseases associate with AS, and the beneficial side effects of B cell subset depleting (modifying) therapies on atherosclerotic concomitant disease, have been observed. Moreover, the CANTOS study (NCT01327846) showed impressive results of immune-mediated inflammation as a new promising target of action for the fight against atherosclerotic endpoints. This review will reflect the putative role of B cells in AS in an attempt to connect observations from animal models with the small spectrum of the thus far available human data. We will also discuss the clinical therapeutic potency of B cell modulations on the process of AS.

scholarly journals Hyper‐metabolic B cells in the spleens of old mice make antibodies with autoimmune specificities

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Daniela Frasca ◽  
Maria Romero ◽  
Denisse Garcia ◽  
Alain Diaz ◽  
Bonnie B. Blomberg
Keyword(s):  
B Cells ◽  
B Cell ◽  
Inflammatory Markers ◽  
Cell Subset ◽  
Antibody Responses ◽  
Metabolic Phenotype ◽  
Cellular Mechanisms ◽  
Autoimmune Antibodies ◽  
B Cell Subsets ◽  
Old Mice

Abstract Background Aging is associated with increased intrinsic B cell inflammation, decreased protective antibody responses and increased autoimmune antibody responses. The effects of aging on the metabolic phenotype of B cells and on the metabolic programs that lead to the secretion of protective versus autoimmune antibodies are not known. Methods Splenic B cells and the major splenic B cell subsets, Follicular (FO) and Age-associated B cells (ABCs), were isolated from the spleens of young and old mice and left unstimulated. The RNA was collected to measure the expression of markers associated with intrinsic inflammation and autoimmune antibody production by qPCR. B cells and B cell subsets were also stimulated with CpG and supernatants collected after 7 days to measure autoimmune IgG secretion by ELISA. Metabolic measures (oxygen consumption rate, extracellular acidification rate and glucose uptake) were performed using a Seahorse XFp extracellular flux analyzer. Results Results have identified the subset of ABCs, whose frequencies and numbers increase with age and represent the most pro-inflammatory B cell subset, as the cell type mainly if not exclusively responsible for the expression of inflammatory markers and for the secretion of autoimmune antibodies in the spleen of old mice. Hyper-inflammatory ABCs from old mice are also hyper-metabolic, as compared to those from young mice and to the subset of FO B cells, a feature needed not only to support their higher expression of RNA for inflammatory markers but also their higher autoimmune antibody secretion. Conclusions These results identify a relationship between intrinsic inflammation, metabolism and autoimmune B cells and suggest possible ways to understand cellular mechanisms that lead to the generation of pathogenic B cells, that are hyper-inflammatory and hyper-metabolic, and secrete IgG antibodies with autoimmune specificities.

scholarly journals Dimethyl fumarate as a first- vs second-line therapy in MS

2018 ◽  
Vol 5 (6) ◽  
pp. e508 ◽  
Author(s):  
Elsebeth Staun-Ram ◽  
Eiman Najjar ◽  
Anat Volkowich ◽  
Ariel Miller
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Plasma Cells ◽  
Dimethyl Fumarate ◽  
Functional Markers ◽  
Immunomodulatory Effects ◽  
Immune Profile ◽  
Line Therapy ◽  
B Cell Subsets

ObjectiveTo elucidate the immunomodulatory effects of dimethyl fumarate (DMF) on B cells in patients with relapsing MS receiving DMF as a “1st-line” vs “2nd-line” therapy.MethodsB cells were isolated from 43 patients with MS at baseline and after 15-week DMF therapy. Phenotype and functional markers and cytokine profile were assessed by flow cytometry. Analysis included clinical and MRI parameters recorded during a 1-year follow-up.Results1st-line and 2nd-line patients presented several differences in their baseline immune profile, which corresponded with differences in their immunologic response to DMF treatment. DMF reduced the proportions of B cells and CD8 T cells whereas increased monocytes. DMF reduced memory B cells, including plasma cells in 2nd-line patients only, whereas strongly increased transitional B cells. Several IL10+ B-cell subsets and TGFβ+ B cells were increased. Proinflammatory LTα+ and TNFα+ B cells were reduced, while IL4+ B cells elevated, whereas IFNγ+ B cells showed opposite effects in 1st-line and 2nd-line patients. HLA and ICAM-1 expression was increased, but % CD86+ B cells reduced. The expression of B-cell activating factor receptor and the proportion of activated CD69 B cells were increased.ConclusionsDMF is associated with increased transitional and IL10+ and TGFβ+ regulatory B cells and a shift toward a more anti-inflammatory immune profile. Cell activation with reduced costimulatory capacity may induce immune hyporesponsiveness. Carryover effects of preceding therapies in 2nd-line patients and the stage of disease influence the immune profile of the patients and the immunomodulatory effects of DMF.

scholarly journals Proportions of B-cell subsets are altered in incomplete systemic lupus erythematosus and correlate with interferon score and IgG levels

Rheumatology ◽  
2020 ◽  
Vol 59 (9) ◽  
pp. 2616-2624
Author(s):  
Svenja Henning ◽  
Wietske M Lambers ◽  
Berber Doornbos-van der Meer ◽  
Wayel H Abdulahad ◽  
Frans G M Kroese ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Subset ◽  
Cross Sectional Study ◽  
Type I ◽  
Healthy Controls ◽  
Sectional Study ◽  
Cross Sectional ◽  
B Cell Subsets

Abstract Objectives Incomplete SLE (iSLE) patients display symptoms typical for SLE but have insufficient criteria to fulfil the diagnosis. Biomarkers are needed to identify iSLE patients that will progress to SLE. IFN type I activation, B-cell-activating factor (BAFF) and B-cell subset distortions play an important role in the pathogenesis of SLE. The aim of this cross-sectional study was to investigate whether B-cell subsets are altered in iSLE patients, and whether these alterations correlate with IFN scores and BAFF levels. Methods iSLE patients (n = 34), SLE patients (n = 41) with quiescent disease (SLEDAI ≤4) and healthy controls (n = 22) were included. Proportions of B-cell subsets were measured with flow cytometry, IFN scores with RT-PCR and BAFF levels with ELISA. Results Proportions of age-associated B-cells were elevated in iSLE patients compared with healthy controls and correlated with IgG levels. In iSLE patients, IFN scores and BAFF levels were significantly increased compared with healthy controls. Also, IFN scores correlated with proportions of switched memory B-cells, plasma cells and IgG levels, and correlated negatively with complement levels in iSLE patients. Conclusion In this cross-sectional study, distortions in B-cell subsets were observed in iSLE patients and were correlated with IFN scores and IgG levels. Since these factors play an important role in the pathogenesis of SLE, iSLE patients with these distortions, high IFN scores, and high levels of IgG and BAFF may be at risk for progression to SLE.

scholarly journals B Cell Subsets as Severity-Associated Signatures in COVID-19 Patients

2020 ◽  
Vol 11 ◽  
Author(s):  
Víctor A. Sosa-Hernández ◽  
Jiram Torres-Ruíz ◽  
Rodrigo Cervantes-Díaz ◽  
Sandra Romero-Ramírez ◽  
José C. Páez-Franco ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Subset ◽  
Hierarchical Cluster ◽  
Specific Subset ◽  
Respiratory Parameters ◽  
Cell Subpopulations ◽  
Severity Of The Disease ◽  
B Cell Subsets ◽  
Relationship Of

BackgroundSARS-CoV-2 infection represents a global health problem that has affected millions of people. The fine host immune response and its association with the disease course have not yet been fully elucidated. Consequently, we analyze circulating B cell subsets and their possible relationship with COVID-19 features and severity.MethodsUsing a multiparametric flow cytometric approach, we determined B cell subsets frequencies from 52 COVID-19 patients, grouped them by hierarchical cluster analysis, and correlated their values with clinical data.ResultsThe frequency of CD19+ B cells is increased in severe COVID-19 compared to mild cases. Specific subset frequencies such as transitional B cell subsets increase in mild/moderate cases but decrease with the severity of the disease. Memory B compartment decreased in severe and critical cases, and antibody-secreting cells are increased according to the severity of the disease. Other non-typical subsets such as double-negative B cells also showed significant changes according to disease severity. Globally, these differences allow us to identify severity-associated patient clusters with specific altered subsets. Finally, respiratory parameters, biomarkers of inflammation, and clinical scores exhibited correlations with some of these subpopulations.ConclusionsThe severity of COVID-19 is accompanied by changes in the B cell subpopulations, either immature or terminally differentiated. Furthermore, the existing relationship of B cell subset frequencies with clinical and laboratory parameters suggest that these lymphocytes could serve as potential biomarkers and even active participants in the adaptive antiviral response mounted against SARS-CoV-2.

scholarly journals PTIP chromatin regulator controls development and activation of B cell subsets to license humoral immunity in mice

2017 ◽  
Vol 114 (44) ◽  
pp. E9328-E9337 ◽  
Author(s):  
Dan Su ◽  
Stijn Vanhee ◽  
Rebeca Soria ◽  
Elin Jaensson Gyllenbäck ◽  
Linda M. Starnes ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Humoral Immunity ◽  
Cell Activation ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Transactivation Domain ◽  
B Cell Activation ◽  
Chromatin Regulator ◽  
B Cell Subsets

B cell receptor signaling and downstream NF-κB activity are crucial for the maturation and functionality of all major B cell subsets, yet the molecular players in these signaling events are not fully understood. Here we use several genetically modified mouse models to demonstrate that expression of the multifunctional BRCT (BRCA1 C-terminal) domain-containing PTIP (Pax transactivation domain-interacting protein) chromatin regulator is controlled by B cell activation and potentiates steady-state and postimmune antibody production in vivo. By examining the effects of PTIP deficiency in mice at various ages during ontogeny, we demonstrate that PTIP promotes bone marrow B cell development as well as the neonatal establishment and subsequent long-term maintenance of self-reactive B-1 B cells. Furthermore, we find that PTIP is required for B cell receptor- and T:B interaction-induced proliferation, differentiation of follicular B cells during germinal center formation, and normal signaling through the classical NF-κB pathway. Together with the previously identified role for PTIP in promoting sterile transcription at the Igh locus, the present results establish PTIP as a licensing factor for humoral immunity that acts at several junctures of B lineage maturation and effector cell differentiation by controlling B cell activation.

Analyzing primary Hodgkin and Reed-Sternberg cells to capture the molecular and cellular pathogenesis of classical Hodgkin lymphoma

Blood ◽  
2012 ◽  
Vol 120 (23) ◽  
pp. 4609-4620 ◽  
Author(s):  
Enrico Tiacci ◽  
Claudia Döring ◽  
Verena Brune ◽  
Carel J. M. van Noesel ◽  
Wolfram Klapper ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Transcriptional Analysis ◽  
Epstein Barr Virus Infection ◽  
Classical Hodgkin Lymphoma ◽  
Barr Virus ◽  
A Genome ◽  
Epstein Barr ◽  
Barr Virus Infection ◽  
B Cell Subsets

Abstract The pathogenesis of classical Hodgkin lymphoma (cHL), the most common lymphoma in the young, is still enigmatic, largely because its Hodgkin and Reed-Sternberg (HRS) tumor cells are rare in the involved lymph node and therefore difficult to analyze. Here, by overcoming this technical challenge and performing, for the first time, a genome-wide transcriptional analysis of microdissected HRS cells compared with other B-cell lymphomas, cHL lines, and normal B-cell subsets, we show that they differ extensively from the usually studied cHL cell lines, that the lost B-cell identity of cHLs is not linked to the acquisition of a plasma cell-like gene expression program, and that Epstein-Barr virus infection of HRS cells has a minor transcriptional influence on the established cHL clone. Moreover, although cHL appears a distinct lymphoma entity overall, HRS cells of its histologic subtypes diverged in their similarity to other related lymphomas. Unexpectedly, we identified 2 molecular subgroups of cHL associated with differential strengths of the transcription factor activity of the NOTCH1, MYC, and IRF4 proto-oncogenes. Finally, HRS cells display deregulated expression of several genes potentially highly relevant to lymphoma pathogenesis, including silencing of the apoptosis-inducer BIK and of INPP5D, an inhibitor of the PI3K-driven oncogenic pathway.

Long Term Humoral Immune Reconstitution Kinetics After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) In Children

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4627-4627
Author(s):  
Amro Elshoury ◽  
Neena Kapoor ◽  
Ami J Shah ◽  
Bhakti Mehta ◽  
Kris M. Mahadeo ◽  
...  
Keyword(s):  
B Cells ◽  
Serum Level ◽  
B Cell ◽  
Immune Reconstitution ◽  
Serum Levels ◽  
Multivariate Regression Analysis ◽  
Memory B Cells ◽  
Post Transplantation ◽  
Humoral Immune ◽  
Cell Counts

Background HSCT recipients have increased incidence of acquiring infections, particularly by encapsulated bacteria such as Streptococcal pneumoniae and Haemophilus influenzae. Delayed immune reconstitution has a pivotal role in these complications. Although T-cell immune reconstitution has been well studied, long-term B-cell reconstitution remains less characterized. Patients and Methods We studied 73 patients, who received allogeneic HSCT at Childrens Hospital Los Angeles. Patients were in complete remission of their underlying disorder and with median follow up 4.15 years [yrs] (range 6 month -18yrs, mean 5 yrs) post-HSCT. All subjects were< 18 years of age. B (naive [IgD+CD27-CD19+], memory [IgD+CD27+CD19+] and switched memory [IgD-CD27+CD19]); and T (CD3+, CD3+CD4+, CD3+CD8+, CD4+CD25+CD127dim (T Regulatory) [Tregs], RA+CD4+) cell subtypes, quantitative Immunoglobulins levels and antibodies to both polyribosyle polyphospate (PRP) and tetanus toxoid (TT) antigens were assessed longitudinally after HSCT. Results Naive B Cells were the first B cell subtype to return to normal value at 6 month post-HSCT, while memory B cells were persistently low up to two years post-HSCT. PRP levels continued to be low up to 10 years post -HSCT in unrelated donor HSCT recipients. TT antibodies level was normal at 6 month post-HSCT following immunization with TT in patients not receiving IVIG therapy. Switched memory B cell counts correlated positively with RA+CD4+ counts at 6 month post-HSCT (r=0.459, P=0.021) and with CD3+CD+4 counts at 6 months (r=0.530, P=0.006) and 2-years post-HSCT (r=0.398, P=0.016). However, switched memory B cells did not correlate with Tregs at any time post-HSCT. Switched memory B cells correlated positively with serum level of IgG at 1 (r=0.443, P=0.039), and 2 years post transplantation (r=0.617, P=0.001) and with serum level of IgA at 2 years post-HSCT(r=0.567. P=0.004). Memory B-cells counts correlated positively with serum levels of IgM at 1 year post-HSCT (r=0.478, P=0.021) and with serum levels of both IgG and IgA (r=0.431 P=0.035, and r=0.416, P=0.043, respectively) at 2 years post-HSCT. However, memory B-cell counts did not correlate with RA+CD4+, CD3+CD4+, CD3+CD8+ or Tregs cell counts. The use of Total body irradiation (TBI) was associated with lower switched memory B cells at 2 years (P=0.01) post-HSCT. TBI recipients also have lower PRP levels at 6-month post-HSCT compared to patients who did not receive TBI. Age of the recipient at time transplantation is another independent factor affecting all the B cell subsets recovery after transplantation; increase in age at transplantation is associated with lower B cell recovery. Decreased memory B cells post-HSCT was observed in patients with history of acute graft versus host disease (GVHD) (P=0.034) and chronic GVHD (P=0.01), even after resolution of clinical manifestations of active GVHD at 6 month and 2 years follow up, respectively. Compared to cord blood graft recipients, Bone marrow graft recipients have increased switched memory B-cells at 6 month and higher (P=0.0001) PRP antibodies titer at 3 years post-HSCT, respectively. Patients who did not receive ATG or Alemtuzumab have increased recovery of naive B-cells (P=0.024) at 2 years post-transplantation. Patients received ATG have higher both naive B cells in univariate analysis and PRP levels (in multivariate analysis) than those received Alemtuzumab at 6 months post-HSCT. Multivariate regression analysis showed that patients received Alemtuzumab have higher TT antibodies titer at 6 month post -HSCT compared to those received ATG. Conclusion We have found that memory and switched memory B-cells and serum PRP levels are deficient post-HSCT in children. Switched memory B cells correlated positively with serum level of IgG and IgA and memory B-cells correlated positively with serum levels of IgM, IgG and IgA. This confirms that HSCT recipients have impaired humoral immune reconstitution, hindering both B-cells development and generation of immunoglobulins. We also studied the different factors affecting humoral immune reconstitution using backwards multivariate regression analysis model and found that the use of TBI, age of the recipient at transplantation, GVHD status and source of stem cells can affect the kinetics of humoral immune reconstitution after HSCT in children. Disclosures: No relevant conflicts of interest to declare.

Long Non-Coding RNAs Are Commonly Deregulated In Hodgkin Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 628-628
Author(s):  
Masoumeh Tayari ◽  
Klaas Kok ◽  
Gertrud Kortman ◽  
Jantine Sietzema ◽  
Debora de Jong ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Differential Expression ◽  
Potential Function ◽  
Expression Pattern ◽  
Differentially Expressed ◽  
Lncrna Expression ◽  
Non Coding Rnas ◽  
B Cell Subsets

Abstract Hodgkin’s lymphoma (HL) is a B-cell neoplasm characterized by a minority of neoplastic cells within an extensive inflammatory background. Long non-coding RNAs (lncRNAs) have diverse roles in transcriptional, posttranscriptional and epigenetic mechanisms in normal cell physiology. Deregulation of lncRNA expression has been implicated in a number of cancers. Up to date it is unclear to what extent lncRNAs are involved in the pathogenesis of Hodgkin lymphoma (HL). We designed a custom made microarray based on a published lncRNA catalog of 10,509 lncRNA loci (Cabili et al., 2011). The array also contains probes for all protein coding genes allowing simultaneous detection of the lncRNA and mRNA expression pattern. We analyzed 6 HL cell lines and three samples of purified tonsillar naive, germinal center (GC) and memory B cells. To get more insight into the potential function of individual differentially expressed lncRNAs we determined lncRNA enrichment in cytoplasmic and nuclear fractions of two HL cell lines. Furthermore, we studied to what extent lncRNAs are enriched in the Argonaute 2 (Ago2) containing complexes as an indication for interaction with miRNAs. In a comparison between the three different normal B-cell subsets, we observed 565 differentially expressed lncRNA probes. Overall, naive and memory B cell subsets showed a highly similar expression pattern while GC B cells showed a distinct lncRNA expression pattern. A significant differential expression between HL and normal GC B-cells was observed for 717 lncRNA probes. Interestingly, 109 of those overlap with the 565 lncRNAs differentially expressed between the normal B cell subsets. Differential expression for 4 in HL up and 2 downregulated lncRNAs was confirmed using qRT-PCR. To get a first indication about their potential function, we evaluated the subcellular location of the lncRNAs by comparing the abundance in nuclear and cytoplasmic fractions relative to the total fraction. Overall, 26% of the expressed lncRNAs were consistently enriched in the nuclear fraction and 10% were predominantly enriched in the cytoplasmic fraction. Of the 717 differentially expressed lncRNAs 82 were consistently enriched in the nucleus and 16 in the cytoplasm. Our Ago2 pull-down experiments revealed that 9% of the mRNAs and 3% of the expressed lncRNAs are consistently enriched in Ago2 complexes. In total, we observed evidence for miRNA binding for 17 of the in HL differentially expressed lncRNAs. In conclusion, we identified a specific lncRNA expression pattern in GC B cells and observed for more than 700 lncRNAs a differentially expression pattern between HL and normal GC B-cells. For 98 lncRNAs we found a specific subcellular enrichment and for 17 we observed enrichment in the Ago2 fraction, indicative of miRNA-lncRNA interactions. Follow-up studies will determine to what extent these lncRNAs contribute to the pathogenesis of Hodgkin lymphoma. Disclosures: No relevant conflicts of interest to declare.

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