scholarly journals Establishment and characterization of a human plasma cell myeloma culture having a rearranged cellular myc proto-oncogene

Blood ◽  
1986 ◽  
Vol 67 (6) ◽  
pp. 1542-1549 ◽  
Author(s):  
AF Gazdar ◽  
HK Oie ◽  
IR Kirsch ◽  
GF Hollis
Keyword(s):  
Cell Line ◽  
Human Plasma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Cultured Cells ◽  
Human Cell Line ◽  
Defined Medium ◽  
Chromosome 8 ◽  
Nuclear Antigen ◽  
Secretory Cells

Using a serum-free defined medium, we have established a human cell line, NCI-H929, from a malignant effusion occurring in a patient with IgAk myeloma. The cultured cells have the morphologic, ultrastructural, biochemical, immunologic, and cytochemical features of plasma cells. The cells have rearranged alpha and kappa genes and synthesize and secrete high amounts of IgAk (greater than 80 micrograms/10(6) cells per 24 hours). The cells express surface immunoglobulin (alpha and kappa), the plasma cell antigen PCA-1, the transferrin receptor (T9) and T10 but lack antigens associated with earlier stages of B cell development (HLA-DR, B1, B2, B4, CALLA), as well as other leukocyte- macrophage antigens and Epstein-Barr virus (EBV) nuclear antigen. Although molecular studies confirm that both the tumor and cultured cells are derived from the same clone of malignant B cells, the tumor cells were predominantly near-diploid, whereas the cultured cells are predominantly near-tetraploid with six copies of chromosome 8, four to six of which have an 8q + abnormality. However, both the tumor and the cultured cells have a rearrangement of the cellular c-myc proto- oncogene (located at 8q24) and express c-myc RNA. Although a modest number of human “plasmacytoid” cell lines have been established, most are lymphoblastoid lines lacking plasma cell features, while others appear to be early secretory cells. In contrast, NCI-H929 is a differentiated, highly secretory human plasma cell line.

scholarly journals Establishment and characterization of a human plasma cell myeloma culture having a rearranged cellular myc proto-oncogene

Blood ◽  
1986 ◽  
Vol 67 (6) ◽  
pp. 1542-1549 ◽  
Author(s):  
AF Gazdar ◽  
HK Oie ◽  
IR Kirsch ◽  
GF Hollis
Keyword(s):  
Cell Line ◽  
Human Plasma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Cultured Cells ◽  
Human Cell Line ◽  
Defined Medium ◽  
Chromosome 8 ◽  
Nuclear Antigen ◽  
Secretory Cells

Abstract Using a serum-free defined medium, we have established a human cell line, NCI-H929, from a malignant effusion occurring in a patient with IgAk myeloma. The cultured cells have the morphologic, ultrastructural, biochemical, immunologic, and cytochemical features of plasma cells. The cells have rearranged alpha and kappa genes and synthesize and secrete high amounts of IgAk (greater than 80 micrograms/10(6) cells per 24 hours). The cells express surface immunoglobulin (alpha and kappa), the plasma cell antigen PCA-1, the transferrin receptor (T9) and T10 but lack antigens associated with earlier stages of B cell development (HLA-DR, B1, B2, B4, CALLA), as well as other leukocyte- macrophage antigens and Epstein-Barr virus (EBV) nuclear antigen. Although molecular studies confirm that both the tumor and cultured cells are derived from the same clone of malignant B cells, the tumor cells were predominantly near-diploid, whereas the cultured cells are predominantly near-tetraploid with six copies of chromosome 8, four to six of which have an 8q + abnormality. However, both the tumor and the cultured cells have a rearrangement of the cellular c-myc proto- oncogene (located at 8q24) and express c-myc RNA. Although a modest number of human “plasmacytoid” cell lines have been established, most are lymphoblastoid lines lacking plasma cell features, while others appear to be early secretory cells. In contrast, NCI-H929 is a differentiated, highly secretory human plasma cell line.

Light Chain Shifting: Identification of a Human Plasma Cell Line Actively Undergoing Light Chain Replacement

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 198-207 ◽  
Author(s):  
Hirofumi Tachibana ◽  
Hirotaka Haruta ◽  
Koji Yamada
Keyword(s):  
Cell Line ◽  
Human Plasma ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
High Rate ◽  
Cell Phenotype ◽  
Recombination Activating Genes ◽  
Λ Light Chain ◽  
Rag 1

Abstract We identified an antibody-secreting human B-cell line (HTD8), which actively replaces the production of the original λ light chain with a new λ chain (light chain shifting) at a high rate. Loss of the original rearranged λ light chain occurs by significantly reducing the amount of transcript expressed. Expression of the new λ chain, which replaces the original λ chain, occurs by rearranging new VJ segments on a previously excluded allele. V λ gene usage of these new rearrangements are biased toward Vλ4, Vλ6, and Vλ10 families, which are known to be the least frequently used. In striking contrast to the plasma cell phenotype, recombination activating genes, RAG-1 and RAG-2, were expressed in the HTD8 cells and were shown to be necessary, but insufficient for inducing expression of the new λ chain. These results suggest that human plasma cells have the potential to actively undergo light chain replacement.

Light Chain Shifting: Identification of a Human Plasma Cell Line Actively Undergoing Light Chain Replacement

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 198-207
Author(s):  
Hirofumi Tachibana ◽  
Hirotaka Haruta ◽  
Koji Yamada
Keyword(s):  
Cell Line ◽  
Human Plasma ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
High Rate ◽  
Cell Phenotype ◽  
Recombination Activating Genes ◽  
Λ Light Chain ◽  
Rag 1

We identified an antibody-secreting human B-cell line (HTD8), which actively replaces the production of the original λ light chain with a new λ chain (light chain shifting) at a high rate. Loss of the original rearranged λ light chain occurs by significantly reducing the amount of transcript expressed. Expression of the new λ chain, which replaces the original λ chain, occurs by rearranging new VJ segments on a previously excluded allele. V λ gene usage of these new rearrangements are biased toward Vλ4, Vλ6, and Vλ10 families, which are known to be the least frequently used. In striking contrast to the plasma cell phenotype, recombination activating genes, RAG-1 and RAG-2, were expressed in the HTD8 cells and were shown to be necessary, but insufficient for inducing expression of the new λ chain. These results suggest that human plasma cells have the potential to actively undergo light chain replacement.

Gp130 and ras mediated signaling in human plasma cell line INA-6: a cytokine-regulated tumor model for plasmacytoma

2001 ◽  
Vol 2 (1) ◽  
pp. 42-53 ◽  
Author(s):  
Renate Burger ◽  
Andreas Guenther ◽  
Frank Bakker ◽  
Marc Schmalzing ◽  
Sabrina Bernand ◽  
...  
Keyword(s):  
Cell Line ◽  
Human Plasma ◽  
Plasma Cell ◽  
Tumor Model

scholarly journals Establishment and characterization of a human myeloid cell line from Philadelphia chromosome-negative myeloblastic leukemia arising in a patient with myelodysplastic syndrome

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1665-1672
Author(s):  
TM McCarty ◽  
S Rajaraman ◽  
FF Elder ◽  
P Gadson ◽  
EB Thompson
Keyword(s):  
Myelodysplastic Syndrome ◽  
Cell Line ◽  
Cultured Cells ◽  
Specific Antigen ◽  
Philadelphia Chromosome ◽  
Morphological Characteristics ◽  
Nuclear Antigen ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Complement Protein ◽  
Phenotypic Analysis

A new hematopoietic cell line derived from a patient with Philadelphia chromosome (Ph1)-negative myeloblastic leukemia arising from a form of myelodysplastic syndrome (MDS) is described. This cell line, designated TMM, consists of immature cells with the morphological characteristics of young myeloblasts and grows in suspension culture with a doubling time of about 30 hours. By cytochemical analysis the cultured cells were positive for acid phosphatase. They were free of the Epstein-Barr virus-associated nuclear antigen as well as terminal deoxynucleotidyl transferase. Further phenotypic analysis revealed the expression of the myelomonocytic-specific antigen Leu-M1 and receptors for the Fc portion of IgG. Partial differentiation of these cells could be induced by dimethyl sulfoxide, tetradecanoyl phorbol acetate, or hypoxanthine and resulted in cells of the myeloid series expressing lysozyme and receptors for the C3b complement protein. The karyotype was 46,XY, lacked the Ph1 chromosome, and displayed no abnormalities at the light microscopic level. No rearrangement of the bcr-c-abl gene complex was found. This cell line should be useful for studying an important type of the heterogeneous population constituting Ph1-negative myeloblastic leukemia, arising in this instance from MDS, as well as for studying differentiation and proliferation of human pluripotent stem cells.

Replication of measles virus in the human plasma cell leukemia-derived LICR-LON-HMy2 cell line

1989 ◽  
Vol 24 (3) ◽  
pp. 313-320
Author(s):  
Barry Ziola ◽  
Michael Morhart ◽  
Lynn Gilbert ◽  
Brenda Karvonen ◽  
Xiao Ping Chen
Keyword(s):  
Cell Line ◽  
Human Plasma ◽  
Plasma Cell ◽  
Measles Virus ◽  
Plasma Cell Leukemia ◽  
Cell Leukemia

scholarly journals Establishment and characterization of a human myeloid cell line from Philadelphia chromosome-negative myeloblastic leukemia arising in a patient with myelodysplastic syndrome

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1665-1672 ◽  
Author(s):  
TM McCarty ◽  
S Rajaraman ◽  
FF Elder ◽  
P Gadson ◽  
EB Thompson
Keyword(s):  
Myelodysplastic Syndrome ◽  
Cell Line ◽  
Cultured Cells ◽  
Specific Antigen ◽  
Philadelphia Chromosome ◽  
Morphological Characteristics ◽  
Nuclear Antigen ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Complement Protein ◽  
Phenotypic Analysis

Abstract A new hematopoietic cell line derived from a patient with Philadelphia chromosome (Ph1)-negative myeloblastic leukemia arising from a form of myelodysplastic syndrome (MDS) is described. This cell line, designated TMM, consists of immature cells with the morphological characteristics of young myeloblasts and grows in suspension culture with a doubling time of about 30 hours. By cytochemical analysis the cultured cells were positive for acid phosphatase. They were free of the Epstein-Barr virus-associated nuclear antigen as well as terminal deoxynucleotidyl transferase. Further phenotypic analysis revealed the expression of the myelomonocytic-specific antigen Leu-M1 and receptors for the Fc portion of IgG. Partial differentiation of these cells could be induced by dimethyl sulfoxide, tetradecanoyl phorbol acetate, or hypoxanthine and resulted in cells of the myeloid series expressing lysozyme and receptors for the C3b complement protein. The karyotype was 46,XY, lacked the Ph1 chromosome, and displayed no abnormalities at the light microscopic level. No rearrangement of the bcr-c-abl gene complex was found. This cell line should be useful for studying an important type of the heterogeneous population constituting Ph1-negative myeloblastic leukemia, arising in this instance from MDS, as well as for studying differentiation and proliferation of human pluripotent stem cells.

scholarly journals T cell–dependent survival of CD20+ and CD20− plasma cells in human secondary lymphoid tissue

Blood ◽  
2007 ◽  
Vol 109 (11) ◽  
pp. 4856-4864 ◽  
Author(s):  
David R. Withers ◽  
Claudia Fiorini ◽  
Randy T. Fischer ◽  
Rachel Ettinger ◽  
Peter E. Lipsky ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Survival ◽  
Human Plasma ◽  
Plasma Cell ◽  
Lymphoid Tissue ◽  
Plasma Cells ◽  
Complete Loss ◽  
Secondary Lymphoid Tissue ◽  
Anti Cd20

Abstract The signals mediating human plasma cell survival in vivo, particularly within secondary lymphoid tissue, are unclear. Human tonsils grafted into immunodeficient mice were therefore used to delineate the mechanisms promoting the survival of plasma cells. Tonsillar plasma cells were maintained within the grafts and the majority were nonproliferating, indicating a long-lived phenotype. A significant depletion of graft plasma cells was observed after anti-CD20 treatment, consistent with the expression of CD20 by most of the cells. Moreover, anti-CD52 treatment caused the complete loss of all graft lymphocytes, including plasma cells. Unexpectedly, anti-CD3, but not anti-CD154, treatment caused the complete loss of plasma cells, indicating an essential role for T cells, but not CD40-CD154 interactions in plasma cell survival. The in vitro coculture of purified tonsillar plasma cells and T cells revealed a T-cell survival signal requiring cell contact. Furthermore, immunofluorescence studies detected a close association between human plasma cells and T cells in vivo. These data reveal that human tonsil contains long-lived plasma cells, the majority of which express CD20 and can be deleted with anti-CD20 therapy. In addition, an important role for contact-dependent interactions with T cells in human plasma cell survival within secondary lymphoid tissue was identified.

scholarly journals Differential effect of growth hormone and insulin-like growth factor-I, insulin-like growth factor-II, and insulin on Ig production and growth in human plasma cells

Blood ◽  
1994 ◽  
Vol 83 (6) ◽  
pp. 1569-1574 ◽  
Author(s):  
H Kimata ◽  
A Yoshida
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Human Plasma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Thymidine Uptake ◽  
Insulin Like Growth Factor ◽  
Cell Responses ◽  
Factor I ◽  
Igf I

The effect of human growth hormone (GH) and insulin-like growth factor- I (IGF-I), IGF-II, and insulin on human plasma cell responses was studied. GH enhanced Ig production and thymidine uptake in the human plasma cell lines, IM-9 and AF-10. IGF-I, but not IGF-II or insulin, also enhanced Ig production and proliferation in them. However, enhancement by GH was not mediated by IGF-I, because enhancement was blocked by anti-GH antibody (Ab), but not by Ab to IGF-I or IGF-I receptor. Conversely, the enhancement by IGF-I was blocked by either Ab to IGF-I or IGF-I receptor, but not by anti-GH Ab. GH and IGF-I also enhanced production of IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, and IgM and thymidine uptake in PCA-1+ plasma cells generated in vitro. Again, enhancement by GH was specifically blocked by anti-GH Ab, whereas enhancement by IGF-I was specifically blocked by either Ab to IGF-I or IGF-I receptor. These results indicate that GH and IGF-I may play important roles in plasma cell responses.

In Vitro Generation of “Long-Lived” Human Plasma Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2187-2187
Author(s):  
Sophie Stephenson ◽  
Mario Cocco ◽  
Ruth deTute ◽  
Andy Rawstron ◽  
Gina Doody ◽  
...  
Keyword(s):  
Cell Division ◽  
Human Plasma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Cell Lineage ◽  
Bone Marrow Plasma ◽  
Extended Lifespan ◽  
Cell Niche

Abstract Abstract 2187 Plasma cells, the terminal effectors of the B-cell lineage include both short- and long-lived cells. The latter persist for extended periods in the absence of cell division, supported in niche environments. No model system has successfully recapitulated the function of the niche to allow the in vitro generation of long-lived plasma cells. This limits investigation into the factors controlling and targeting plasma cell populations. Here we describe the generation of mature human plasma cells with extended lifespan from peripheral blood B-cells. Cell division accompanies phenotypic maturation between plasmablasts and plasma cells. These cells then persist in the absence of cell division, remaining functional and viable in extended culture, currently limited solely by elective termination. Extended survival is accompanied by maturation to a phenotype consistent with human bone marrow plasma cells. By establishing a set of conditions sufficient to allow the development and persistence of mature human plasma cells in vitro, we recapitulate the essential function of the plasma cell niche. We definitively link phenotypic maturation to lifespan and provide the first platform with which to explore and manipulate the full trajectory of human plasma cell differentiation. Disclosures: No relevant conflicts of interest to declare.

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