scholarly journals The E mu-myc transgenic mouse. A model for high-incidence spontaneous lymphoma and leukemia of early B cells.

1988 ◽  
Vol 167 (2) ◽  
pp. 353-371 ◽  
Author(s):  
A W Harris ◽  
C A Pinkert ◽  
M Crawford ◽  
W Y Langdon ◽  
R L Brinster ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Surface ◽  
Genetic Background ◽  
Constitutive Expression ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Lymphoid Leukemia ◽  
High Incidence ◽  
Myc Gene ◽  
Transplantation Assay

Mice transgenic for a c-myc gene driven by the IgH enhancer (E mu-myc) were shown to almost invariably develop lymphomas, 90% succumbing in the first 5 mo of life. The tumors typically presented as rapidly progressive lymphadenopathy with thymic involvement and were highly malignant by transplantation assay. Morphologically, they were lymphoblastic lymphomas, usually accompanied by lymphoid leukemia and granulocytosis, and were distinct from the tumors that arose much later in 37% of nontransgenic mice of the same (C57BL/6 x SJL)F2 genetic background. Cell-surface markers on 31 E mu-myc tumors identified 52% as pre-B lymphomas, 29% as mixed pre-B and B lymphomas, and 19% as B lymphomas. The tumors appeared to arise at random from a population of pre-B cells expanded by constitutive expression of the myc transgene. A majority of the animals initiated malignancy at the rate of 17% per week. The rate at which the cycling, benign pre-B cells spontaneously convert to malignancy was estimated to about 10(-10) per cell per generation. A transient leukocytosis identified in young E mu-myc mice was developed into a rapid assay for inheritance of the transgene.

Trogocytosis of multiple B-cell surface markers by CD22 targeting with epratuzumab

Blood ◽  
2013 ◽  
Vol 122 (17) ◽  
pp. 3020-3029 ◽  
Author(s):  
Edmund A. Rossi ◽  
David M. Goldenberg ◽  
Rosana Michel ◽  
Diane L. Rossi ◽  
Daniel J. Wallace ◽  
...  
Keyword(s):  
B Cells ◽  
Autoimmune Disease ◽  
Cell Surface ◽  
B Cell ◽  
Regulatory Proteins ◽  
Surface Markers ◽  
B Cell Antigen Receptor ◽  
Cell Surface Markers ◽  
Effector Cells ◽  
Key Points

Key Points Epratuzumab induces the reduction of multiple B-cell antigen receptor–modulating proteins on the surface of B cells via their trogocytosis to effector cells. Modulation of B cells by trogocytosis of key regulatory proteins may be an important mechanism of immunotherapy of autoimmune disease.

Abstract 4744: CD22-targeting epratuzumab mediates trogocytosis of multiple cell-surface markers on normal, malignant, and lupus B cells.

2013 ◽  
Author(s):  
Edmund A. Rossi ◽  
David M. Goldenberg ◽  
Rosana Michel ◽  
Diane L. Rossi ◽  
Daniel J. Wallace ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Surface ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Multiple Cell

scholarly journals Hypothesis: differentiation of the human lymphoid system based on cell surface markers

Blood ◽  
1975 ◽  
Vol 45 (6) ◽  
pp. 871-880
Author(s):  
S Davis
Keyword(s):  
B Cells ◽  
Cell Surface ◽  
Developmental Stages ◽  
Human Lymphocytes ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Characteristic Surface ◽  
T And B Cells ◽  
Lymphoproliferative Diseases ◽  
A Cell

Human lymphocytes can be separated into distinct populations based upon receptors on their cell surface. Thymus-derived (T-cell) lymphocytes can be identified by their ability to form rosetts with sheep erythrocytes (SRBC); bone marrow-derived (B-cell) lymphocytes bear characteristic surface markers for immunoglobulin, complement, and the Fc portion of IgG. Recently, populations of lymphocytes having either multiple markers or no detectable markers (null cells) have been observed. Based on studies of cell surface markers, a scheme is proposed that expands the known differentiation of the lymphod cell to include subpopulations which represent developmental stages. It is suggested that lymphocyte maturation involves alloantigenic changes in a circulating stem cell-drived nill cell, leading to a cell bearing markers for both T- and B-cells. It is from this latter cell that the classic T- and B-cells ultimately arise. Maturational defects which may explain the origin of primary lymphoproliferative diseases are discussed.

scholarly journals Adenosine deaminase, terminal deoxynucleotidyl transferase (TdT), and cell surface markers in childhood acute leukemia

Blood ◽  
1978 ◽  
Vol 52 (6) ◽  
pp. 1125-1131 ◽  
Author(s):  
MS Coleman ◽  
MF Greenwood ◽  
JJ Hutton ◽  
P Holland ◽  
B Lampkin ◽  
...  
Keyword(s):  
Cell Surface ◽  
Adenosine Deaminase ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Null Cell ◽  
Lymphoid Leukemia ◽  
Acute Lymphoid Leukemia ◽  
Activity Measurements ◽  
Adenosine Deaminase Activity

Abstract The purpose of this report is to compare measurements of enzymatic activities and cell surface markers as methods of distinguishing subtypes of lymphoid leukemias of childhood. Twenty-six children ages 2- 15 yr were studied. Terminal deoxynucleotidyl transferase (TdT) activity was high in blasts from all 20 children with either null or T cell acute lymphoblastic leukemia. The activity of adenosine deaminase per cell was higher (P less than 0.005) and that of TdT lower (p less than 0.05) in T than in null cell lymphoblasts, although there was some overlap in values. Blasts from 3 children with acute lymphoid leukemia were positive for surface-associated immunoglobulins. The neoplastic lymphoid cells from these children differed from T and null cell leukemic lymphoblasts by having very low levels of TdT and adenosine deaminase activity. Measurements of adenosine deaminase and TdT may complement measurements of cell surface markers and distinguish biochemical subtypes of acute lymphoid leukemia.

scholarly journals Hypothesis: differentiation of the human lymphoid system based on cell surface markers

Blood ◽  
1975 ◽  
Vol 45 (6) ◽  
pp. 871-880 ◽  
Author(s):  
S Davis
Keyword(s):  
B Cells ◽  
Cell Surface ◽  
Developmental Stages ◽  
Human Lymphocytes ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Characteristic Surface ◽  
T And B Cells ◽  
Lymphoproliferative Diseases ◽  
A Cell

Abstract Human lymphocytes can be separated into distinct populations based upon receptors on their cell surface. Thymus-derived (T-cell) lymphocytes can be identified by their ability to form rosetts with sheep erythrocytes (SRBC); bone marrow-derived (B-cell) lymphocytes bear characteristic surface markers for immunoglobulin, complement, and the Fc portion of IgG. Recently, populations of lymphocytes having either multiple markers or no detectable markers (null cells) have been observed. Based on studies of cell surface markers, a scheme is proposed that expands the known differentiation of the lymphod cell to include subpopulations which represent developmental stages. It is suggested that lymphocyte maturation involves alloantigenic changes in a circulating stem cell-drived nill cell, leading to a cell bearing markers for both T- and B-cells. It is from this latter cell that the classic T- and B-cells ultimately arise. Maturational defects which may explain the origin of primary lymphoproliferative diseases are discussed.

scholarly journals Establishment and Expression of Cytokines in a Theileria annulata-Infected Bovine B Cell Line

Genes ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 329 ◽  
Author(s):  
Rashid ◽  
Guan ◽  
Luo ◽  
Zhao ◽  
Wang ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Cell Line ◽  
Cytokine Production ◽  
Theileria Annulata ◽  
Transformed Cells ◽  
Specific Cell ◽  
Surface Markers ◽  
Cell Surface Markers

This study aimed to establish a pure single-cell Theileria annulata-infected B cell line for the assessment of cytokine production in transformed and lipopolysaccharide (LPS)-stimulated cells. Several studies have aimed to identify cell surface markers in T. annulata-transformed cells; however, no information on cytokine production in these cells is available. To investigate the potential of the transformed cells to produce cytokines and their potential responses to antigen-stimulation, we purified mature B cells (CD21) from the whole blood of cattle experimentally infected with the T. annulata Kashi strain by magnetic separation. The purity and specificity of the established cell line was assessed by the identification of specific cell surface markers (CD21, IgM, and WC4) by flow cytometry analysis. The transcript levels of the cytokines IL1A, IL1B, IL2, IL4, IL6, IL8, IL10, IL16, LTA, TGFB1, TNFA, IFNA, and IFNB in transformed, buparvaquone (BW720c)-treated cells, and antigen-stimulated cells were analyzed by quantitative polymerase chain reaction (qPCR) using cDNA from these cells. A T. annulata-infected bovine B cell line was successfully established with a purity of ~98.8% (CD21). IL4 and IL12A were significantly (p < 0.01) upregulated in the transformed cells. In BW720c-treated transformed cells, IL12B, TGFB1, and IFNB were significantly (p < 0.01) upregulated. Notably, no significant (p > 0.05) upregulation of cytokines was observed in LPS-stimulated transformed cells. Moreover, IL1A, IL1B, IL8, and IL16 were significantly (p < 0.01) upregulated in LPS-stimulated B cells. Our data signify the potential use of this cell line for cytokine production, observance of immunoglobulins, and production of an attenuated vaccine against tropical theileriosis.

scholarly journals Adenosine deaminase, terminal deoxynucleotidyl transferase (TdT), and cell surface markers in childhood acute leukemia

Blood ◽  
1978 ◽  
Vol 52 (6) ◽  
pp. 1125-1131
Author(s):  
MS Coleman ◽  
MF Greenwood ◽  
JJ Hutton ◽  
P Holland ◽  
B Lampkin ◽  
...  
Keyword(s):  
Cell Surface ◽  
Adenosine Deaminase ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Null Cell ◽  
Lymphoid Leukemia ◽  
Acute Lymphoid Leukemia ◽  
Activity Measurements ◽  
Adenosine Deaminase Activity

The purpose of this report is to compare measurements of enzymatic activities and cell surface markers as methods of distinguishing subtypes of lymphoid leukemias of childhood. Twenty-six children ages 2- 15 yr were studied. Terminal deoxynucleotidyl transferase (TdT) activity was high in blasts from all 20 children with either null or T cell acute lymphoblastic leukemia. The activity of adenosine deaminase per cell was higher (P less than 0.005) and that of TdT lower (p less than 0.05) in T than in null cell lymphoblasts, although there was some overlap in values. Blasts from 3 children with acute lymphoid leukemia were positive for surface-associated immunoglobulins. The neoplastic lymphoid cells from these children differed from T and null cell leukemic lymphoblasts by having very low levels of TdT and adenosine deaminase activity. Measurements of adenosine deaminase and TdT may complement measurements of cell surface markers and distinguish biochemical subtypes of acute lymphoid leukemia.

scholarly journals Defining Germline Predisposition to Dnmt3a-Mutant Clonal Hematopoiesis (CH)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1198-1198
Author(s):  
Logan Sari Schwartz ◽  
Kristina Mujica ◽  
Rebecca Bell ◽  
Matthew Loberg ◽  
Jennifer Trowbridge
Keyword(s):  
Cell Surface ◽  
Genetic Background ◽  
Hematologic Malignancy ◽  
Human Populations ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Genetic Contribution ◽  
Hematopoietic Stem ◽  
Clonal Hematopoiesis ◽  
Functional Potential

Clonal hematopoiesis (CH) is the result of somatic mutations that confer a selective advantage to hematopoietic stem cells (HSCs), driving them to outcompete other HSCs and dominate mature hematopoietic cell production. While it is estimated that by middle age nearly all healthy individuals will have low but detectable variant allele frequency (VAF) indicating CH, only a small fraction will progress to hematologic malignancy. No methods currently exist to predict who will or will not progress to hematologic malignancy and preventative therapeutic strategies are lacking, largely due to poor understanding of the risk factors that determine whether individuals are susceptible to, or protected from, CH. Several recent population sequencing studies have found that inherited genetic variants increase the likelihood of developing CH and that there are population differences in clonal advantages gained by specific mutations in particular genetic and environmental contexts. Limitations of these human studies are the insufficient ability to control for and distinguish genetic from environmental contributions to CH, and to directly interrogate mechanisms causing genetic predisposition to CH and progression to malignancy. To overcome these barriers, here we have utilized the eight inbred and wild-derived founder strains of the Collaborative Cross (CC) and Diversity Outbred (DO) mouse populations (Saul MC et al., Trends in Genetics 2019). These feature well-characterized, segregated genetic variation that accurately reflects the genetic structure of human populations in a controlled environment. We crossed our recently described mouse model of CH (Dnmt3aR878H/+Mx1-Cre on a C57BL/6 background) (Loberg MA et al., Leukemia 2019) with each of the eight founder strains. We observed that genetic background conferred sensitivity or resistance to Dnmt3aR878H/+ HSC expansion based on phenotypic cell surface markers (Lin- c-Kit+ Sca-1+ CD150+ CD48-), relative to Dnmt3a+/+Mx1-Cre strain littermate controls. Genetic contribution from the C57BL/6 and CAST strains permitted robust Dnmt3aR878H/+ HSC expansion compared to Dnmt3a+/+ controls over a period of 6 months. In this same time frame, genetic contribution from 129, NOD, NZO, A/J, PWK, WSB strains demonstrated a spectrum of resistance to Dnmt3aR878H/+ HSC expansion. In vitro studies using colony-forming assays of bone marrow cells isolated from selected strains show a positive correlation between serial replating efficiency and phenotypic HSC frequency, supporting that phenotypic cell surface markers reliably define cells with functional potential across these strains. Ongoing studies to interrogate in vivo functional potential by competitive transplantation of HSCs isolated from each of these strains will be discussed. Together, our work demonstrates that HSC expansion as a consequence of Dnmt3a mutation is influenced by heritable genetic background in a controlled environmental setting. Understanding the mechanisms, at the systemic, intracellular and/or molecular levels, by which genetic background modifies HSC expansion caused by Dnmt3a or other CH mutations will be critical to develop improved prognostic tools and therapeutics to diagnose and treat high-risk versus low-risk CH. For this, utilization of genetically diverse mouse populations provides a critically needed platform to determine causative mechanisms driving clonal expansion of HSCs. Disclosures Trowbridge: Fate Therapeutics: Patents & Royalties: patent license.

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