The relative expression levels of CD148 and CD180 on clonal B cells and CD148/CD180 median fluorescence intensity ratios are useful in the characterization of mature B cell lymphoid neoplasms infiltrating blood and bone marrow – Results from a single centre pilot study

2021 ◽  
Author(s):  
Arambam Gautam ◽  
Sreejesh Sreedharanunni ◽  
Man Updesh Singh Sachdeva ◽  
Sonia Rana ◽  
Dharambir Kashyap ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Pilot Study ◽  
B Cell ◽  
Fluorescence Intensity ◽  
Median Fluorescence Intensity ◽  
Single Centre ◽  
Expression Levels ◽  
Intensity Ratios

Immunological Shift On Day 15 of Remission Induction in Children with CD10-Positive B-Cell Precursor ALL Treated by ALL-MB 2008 Protocol.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2650-2650
Author(s):  
Alexander Popov ◽  
Tatiana Verzhbitskaya ◽  
Grigory Tsaur ◽  
Egor Shorikov ◽  
Leonid Saveliev ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Fluorescence Intensity ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Cell Precursor ◽  
Childhood All

Abstract Abstract 2650 Poster Board II-626 Statement. Flow cytometric (FC) minimal residual disease (MRD) monitoring during remission induction is a strong tool for prediction of outcome in children with acute lymphoblastic leukemia (ALL) of B-cell precursor (BCP) origin. Antigens' expression changes during treatment. Immunological shift can significantly complicate MRD detection. Immunophenotypical changes could vary during antileukemic treatment. Aim. To compare CD19, CD10, CD34, CD20, CD45 and CD58 expression at diagnosis and on day 15 of remission induction of currently applied ALL-MB 2008 treatment protocol and to evaluate significance of this changes for FC MRD monitoring. Patients and methods. Since November 2008 till July 2009 38 cases of childhood ALL were enrolled onto ALL-MB 2008 trial in Pediatric Oncology and Hematology Center in Ekaterinburg. Among them 22 patients were selected for present study as they fulfilled following criteria: had CD10-positive BCP-ALL and were MRD-positive ≥ 10−4 on day 15. MRD detection in bone marrow was performed by 9-color FC. We compared mean fluorescence intensity (MFI) values at diagnosis and on day 15. We also analyzed changes in CD19, CD20, CD45 and CD58 expression by normal B-lymphocytes on day 15 because at this time-point B-lineage regeneration is absent in bone marrow and MRD has to be discriminated only from mature B-cells. Coefficient of variation (CV) of fluorescence intensity and percentage of positive cells were used for evaluation of cells' distribution changes. Results. At diagnosis we found significant differences in antigen expression between tumor cells and B-lymphocytes. CD10, CD34, CD58 overexpression and CD19, CD20, CD45 underexpression by leukemic blasts were noted. On day 15 CD10, CD34 and CD58 were downmodulated (p = 0,0030, p = 0,0007 and p = 0,0017 respectively) while CD19, CD20 and CD45 were upmodulated (p = 0,0033, p = 0,0273 and p = 0,0001 respectively). At the same time CD20, CD45 and CD58 expression by mature B-lymphocytes decreased (p = 0,0013, p = 0,0130 and p = 0,0067 respectively) while CD19 was stable (p = 0,1060). Hence malignant and normal cells became closer on dot plots. On day 15 significant differences in CD10, CD34, CD20, CD45 and CD58 between blasts and lymphocytes were still presented. CD19 expression by leukemic cells on day 15 became higher than by mature B-cells (median MFI = 20284, range1587-34505 and median MFI = 15823, range 811–30882, p = 0,0196). Cells' distribution by CD10 and CD34 became more heterogeneous (p = 0,0364 and p = 0,0008 respectively), CD45 expression became more homogeneous (p = 0,0003) while CD20 and CD58 expression CV didn't change significantly (p = 0,1913 and p = 0,3443 respectively). CD20- and CD45-positive cells' percentage increased (p = 0,0015 and p = 0,0002 respectively) and CD34-positive cells' percentages decreased (p = 0,0003). Discussion. Changes in antigens' expression could complicate MRD detection so far as they decrease immunophenotypical differences between tumor blasts and mature B-lymphocytes. Interestingly, disparity of our results and previously shown data was found. Differences in immunological shift could be partially explained by differences in induction intensity of ALL-MB 2008 and international protocols. Conclusion. Significant immunological shift occurred on day 15 of ALL-MB 2008 remission induction. These antigens' expression changes have to be taken into account by the researcher for the successful FC MRD monitoring. Disclosures: No relevant conflicts of interest to declare.

The expression of Vpre-B/λ5 surrogate light chain in early bone marrow precursor B cells of normal and B cell-deficient mutant mice

Cell ◽  
1994 ◽  
Vol 77 (1) ◽  
pp. 133-143 ◽  
Author(s):  
Hajime Karasuyama ◽  
Antonius Rolink ◽  
Yoichi Shinkal ◽  
Faith Young ◽  
Frederick W. Alt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Light Chain ◽  
Mutant Mice ◽  
Deficient Mutant ◽  
Surrogate Light Chain ◽  
Bone Marrow Precursor ◽  
Precursor B Cells

Transformation of murine bone marrow cells with combined v-raf-v-myc oncogenes yields clonally related mature B cells and macrophages

1990 ◽  
Vol 10 (7) ◽  
pp. 3562-3568
Author(s):  
M Principato ◽  
J L Cleveland ◽  
U R Rapp ◽  
K L Holmes ◽  
J H Pierce ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Bone Marrow Cells ◽  
Hematopoietic Differentiation ◽  
Developmental Relationships ◽  
Murine Bone Marrow ◽  
B Lineage ◽  
Marrow Cells

Murine bone marrow cells infected with replication-defective retroviruses containing v-raf alone or v-myc alone yielded transformed pre-B cell lines, while a retroviral construct containing both v-raf and v-myc oncogenes produced clonally related populations of mature B cells and mature macrophages. The genealogy of these transformants demonstrates that mature myeloid cells were derived from cells with apparent B-lineage commitment and functional immunoglobulin rearrangements. This system should facilitate studies of developmental relationships in hematopoietic differentiation and analysis of lineage determination.

Antibody Production Remains Intact Despite Loss of Bone Marrow B cells in Murine Norovirus Infected Stat1−/− Mice

2021 ◽  
Author(s):  
Daniel E Eldridge ◽  
Charlie C Hsu
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Cell Loss ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Murine Norovirus ◽  
Laboratory Mice ◽  
T And B Cells ◽  
Humoral Immune

Murine norovirus (MNV), which can be used as a model system to study human noroviruses, can infect macrophages/monocytes, neutrophils, dendritic, intestinal epithelial, T and B cells, and is highly prevalent in laboratory mice. We previouslyshowed that MNV infection significantly reduces bone marrow B cell populations in a Stat1-dependent manner. We show here that while MNV-infected Stat1−/− mice have significant losses of bone marrow B cells, splenic B cells capable of mounting an antibody response to novel antigens retain the ability to expand. We also investigated whether increased granulopoiesis after MNV infection was causing B cell loss. We found that administration of anti-G-CSF antibody inhibits the pronounced bone marrow granulopoiesis induced by MNV infection of Stat1−/− mice, but this inhibition did not rescue bone marrow B cell losses. Therefore, MNV-infected Stat1−/− mice can still mount a robust humoral immune response despite decreased bone marrow B cells. This suggests that further investigation will be needed to identify other indirect factors or mechanisms that are responsible for the bone marrow B cell losses seen after MNV infection. In addition, this work contributes to our understanding of the potential physiologic effects of Stat1-related disruptions in research mouse colonies that may be endemically infected with MNV.

scholarly journals TP53INP1 deficiency maintains murine B lymphopoiesis in aged bone marrow through redox-controlled IL-7R/STAT5 signaling

2018 ◽  
Vol 116 (1) ◽  
pp. 211-216 ◽  
Author(s):  
Bochra Zidi ◽  
Christelle Vincent-Fabert ◽  
Laurent Pouyet ◽  
Marion Seillier ◽  
Amelle Vandevelde ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Immune Cell ◽  
B Lymphopoiesis ◽  
Hematopoietic Stem ◽  
Chronic Oxidative Stress ◽  
The Impact ◽  
Deficient Mice

Bone marrow (BM) produces all blood and immune cells deriving from hematopoietic stem cells (HSCs). The decrease of immune cell production during aging is one of the features of immunosenescence. The impact of redox dysregulation in BM aging is still poorly understood. Here we use TP53INP1-deficient (KO) mice endowed with chronic oxidative stress to assess the influence of aging-associated redox alterations in BM homeostasis. We show that TP53INP1 deletion has no impact on aging-related accumulation of HSCs. In contrast, the aging-related contraction of the lymphoid compartment is mitigated in TP53INP1 KO mice. B cells that accumulate in old KO BM are differentiating cells that can mature into functional B cells. Importantly, this phenotype results from B cell-intrinsic events associated with defective redox control. Finally, we show that oxidative stress in aged TP53INP1-deficient mice maintains STAT5 expression and activation in early B cells, driving high Pax5 expression, which provides a molecular mechanism for maintenance of B cell development upon aging.

scholarly journals COMPARISON OF CHROMOSOMAL REARRANGEMENTS IN BONE MARROW CELLS AND BLAST TRANSFORMED B-CELLS IN RELAPSE OF B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA/ SMALL LYMPHOCYTIC LYMPHOMA

2017 ◽  
Vol 39 (2) ◽  
pp. 141-144
Author(s):  
S V Andreieva ◽  
K V Korets ◽  
O E Ruzhinska ◽  
I M Skorokhod ◽  
O G Alkhimova
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Chromosomal Rearrangements ◽  
Lymphocytic Leukemia ◽  
Banding Technique ◽  
Small Lymphocytic Lymphoma ◽  
Detection Frequency ◽  
Cell Chronic Lymphocytic Leukemia

Aim: The genetic mechanisms of resistance to chemotherapy in B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL) are not clear. We aimed to determine the peculiarities of abnormal karyotype formation in bone marrow (BM) cells and peripheral blood (PB) blast transformed B-cells in relapse of B-CLL/SLL. Materials and Methods: Cytogenetic GTG banding technique and molecular cytogenetic in interphase cells (i-FISH) studies of BM cells and PB blast transformed B-lymphocytes were performed in 14 patients (10 males and 4 females) with B-CLL/SLL. Results: The results of karyotyping BM and PB cells revealed the heterogeneity of cytogenetic abnormalities in combined single nosological group of B-CLL/SLL. In PB B-cells, chromosome abnormalities related to a poor prognosis group were registered 2.5 times more often than in BM cells. Additional near tetraploid clones that occurred in 57.1% cases were the peculiar feature of BM cell karyotypes. Chromosomal rearrangements characteristic of the group of adverse cytogenetic prognosis were revealed in all cases from which in 2 cases by karyotyping BM cells, in 6 cases in PB B-cells and in 8 cases by the i-FISH method in BM cells, i.e. their detection frequency was 3 times higher in PB B-cells and 4 times higher when analyzing by i-FISH in BM cells. Conclusions: Mismatch in abnormal karyotypes in BM and PB B-cells by the presence of quantitative and structural chromosomal rearrangements may be indicative of simultaneous and independent processes of abnormal clone formation in the lymph nodes and BM hematopoietic cells. Accumulation the information about previously unidentified chromosomal rearrangements in relapse of the disease may help to understand the ways of resistance formation to chemotherapy.

scholarly journals Mesenchymal Stromal Cells Orchestrate Follicular Lymphoma Cell Niche Through the CCL2-Dependent Recruitment and Polarization of Monocytes

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1566-1566
Author(s):  
Fabien Guilloton ◽  
Gersende Caron ◽  
Cédric Ménard ◽  
Céline Pangault ◽  
Patricia Amé-Thomas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Cell Growth ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Gene Set Enrichment Analysis ◽  
Cell Niche

Abstract Abstract 1566 Accumulating evidence indicates that infiltrating stromal cells contribute directly and indirectly to tumor growth in a wide range of solid cancers and hematological malignancies. In follicular lymphoma (FL), malignant B cells are found admixed with heterogeneous lymphoid-like stromal cells within invaded lymph nodes and bone marrow (BM). In addition, in vitro functional studies have underlined that mesenchymal cells recruit malignant FL B cells and protect them from spontaneous and drug-induced apoptosis. In particular, we have previously demonstrated that mesenchymal stromal cells (MSC) efficiently support in vitro FL B-cell survival, especially after their engagement towards lymphoid differentiation through treatment with TNF-α and Lymphotoxin-α1β2 (TNF/LT) or after coculture with malignant B cells. However, the mechanisms of this supportive activity remain largely unknown. In this study, we used Affymetrix U133 Plus 2.0 microarrays, to compare the gene expression profile (GEP) of bone marrow-derived MSC (BM-MSC) obtained from 10 FL patients at diagnosis versus 6 age-matched healthy donors (HD). In these conditions, neither the CFU-F concentration in the BM nor the cumulative population doubling of BM-MSC significantly differed between HD and FL patients. Unsupervised analysis was able to perfectly segregate FL-MSC from HD-MSC and we identified, using supervised analyzes, a list of 408 probesets defining FL-MSC signature, including 320 nonredundant genes upregulated in FL-MSC compared to HD-MSC. We then defined the GEP of human lymphoid-like stroma using HD-MSC treated in vitro by TNF/LT and demonstrated, by a Gene Set Enrichment Analysis (GSEA) approach, that the FL-MSC signature is significantly enriched for genes associated with a lymphoid-like commitment. Interestingly, CCL2 was strongly overexpressed by FL-MSC, was upregulated in HD-MSC by coculture with malignant B cells, and was detected at a higher level in FL BM plasma compared to normal BM plasma (504.4 pg/mL [23.8-4413] versus 33.9 pg/mL [5-126.1]; P <.01). In agreement, FL-MSC triggered a more potent CCL2-dependent monocyte migration than HD-MSC. Moreover, FL-MSC and macrophages cooperated to sustain malignant B-cell growth through both protection from apoptosis and enhancement of cell proliferation. Finally, FL-MSC promoted monocyte differentiation towards a proangiogenic LPS-unresponsive phenotype close to that of tumor-associated macrophages. We unraveled a key role for the Notch pathway in this process and identified an overexpression of JAGGED1 in FL-MSC compared to HD-MSC. Altogether, these results highlight the complex role of FL stromal cells that promote direct tumor B-cell growth and orchestrate FL cell niche. The identification and characterization of this intricate network of cell interactions may provide novel therapeutic targets in this disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Central human B cell tolerance manifests with a distinctive cell phenotype and is enforced via CXCR4 signaling in hu-mice

2021 ◽  
Vol 118 (16) ◽  
pp. e2021570118
Author(s):  
Thiago Alves da Costa ◽  
Jacob N. Peterson ◽  
Julie Lang ◽  
Jeremy Shulman ◽  
Xiayuan Liang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune System ◽  
B Cells ◽  
B Cell ◽  
Cell Tolerance ◽  
Human Immune System ◽  
B Cell Tolerance ◽  
Autoreactive B Cells ◽  
Cell Clones ◽  
Human Immune

Central B cell tolerance, the process restricting the development of many newly generated autoreactive B cells, has been intensely investigated in mouse cells while studies in humans have been hampered by the inability to phenotypically distinguish autoreactive and nonautoreactive immature B cell clones and the difficulty in accessing fresh human bone marrow samples. Using a human immune system mouse model in which all human Igκ+ B cells undergo central tolerance, we discovered that human autoreactive immature B cells exhibit a distinctive phenotype that includes lower activation of ERK and differential expression of CD69, CD81, CXCR4, and other glycoproteins. Human B cells exhibiting these characteristics were observed in fresh human bone marrow tissue biopsy specimens, although differences in marker expression were smaller than in the humanized mouse model. Furthermore, the expression of these markers was slightly altered in autoreactive B cells of humanized mice engrafted with some human immune systems genetically predisposed to autoimmunity. Finally, by treating mice and human immune system mice with a pharmacologic antagonist, we show that signaling by CXCR4 is necessary to prevent both human and mouse autoreactive B cell clones from egressing the bone marrow, indicating that CXCR4 functionally contributes to central B cell tolerance.

scholarly journals Characterization of human FDCs reveals regulation of T cells and antigen presentation to B cells

2021 ◽  
Vol 218 (10) ◽  
Author(s):  
Balthasar A. Heesters ◽  
Kyah van Megesen ◽  
Ilhan Tomris ◽  
Robert P. de Vries ◽  
Giuliana Magri ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Intimate Contact ◽  
Expression Of Genes ◽  
T Cell Regulation ◽  
Native Antigen ◽  
Reticular Cells ◽  
Molecular Patterns

Stromal-derived follicular dendritic cells (FDCs) are essential for germinal centers (GCs), the site where B cells maturate their antibodies. FDCs present native antigen to B cells and maintain a CXCL13 gradient to form the B cell follicle. Yet despite their essential role, the transcriptome of human FDCs remains undefined. Using single-cell RNA sequencing and microarray, we provided the transcriptome of these enigmatic cells as a comprehensive resource. Key genes were validated by flow cytometry and microscopy. Surprisingly, marginal reticular cells (MRCs) rather than FDCs expressed B cell activating factor (BAFF). Furthermore, we found that human FDCs expressed TLR4 and can alter antigen availability in response to pathogen-associated molecular patterns (PAMPs). High expression of PD-L1 and PD-L2 on FDCs activated PD1 on T cells. In addition, we found expression of genes related to T cell regulation, such as HLA-DRA, CD40, and others. These data suggest intimate contact between human FDCs and T cells.

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