scholarly journals Human J chain gene. Structure and expression in B lymphoid cells.

1985 ◽  
Vol 161 (4) ◽  
pp. 832-849 ◽  
Author(s):  
E E Max ◽  
S J Korsmeyer
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
B Lymphocyte ◽  
Sequence Data ◽  
Regulation Of Gene Expression ◽  
Lymphoid Cells ◽  
Chain Gene ◽  
S1 Nuclease ◽  
J Chain ◽  
B Lymphoid

As part of an ongoing investigation of the regulation of gene expression in B cell development, we have obtained a genomic DNA clone encoding the human J chain protein. The nucleotide sequence of exons encoding the mature protein defines a 137 amino acid primary sequence similar to that previously determined at the protein level. Probes from the gene have been used to analyze J chain expression in human cell lines corresponding to pre-B and B lymphocytes. J chain RNA was detected in two of six human pre-B cell lines and in 8 of 10 B cell lines expressing various Ig isotypes. The expression of the J chain gene is, thus, not tightly linked to IgM or IgA secretion. Our data do not, however, support the recent suggestion (7) that synthesis of J chain precedes that of mu chain in B lymphocyte differentiation. Because of the presence of nine candidate polyadenylation signals (AATAAA or AATTAAA) downstream of the C-terminal coding block of the J chain gene, the 3' end of the gene could not be determined from sequence data alone. To define the 3' end, J chain RNA from a human B lymphocyte line was used to protect an end-labelled DNA fragment from S1 nuclease digestion. The sequence 40 basepairs 5' of the functional polyadenylation site identified by these S1 experiments is homologous the same region of a previously reported mouse J chain complementary DNA clone.

scholarly journals Elevated myc expression and c-myc amplification in spontaneously occurring B lymphoid cell lines.

1987 ◽  
Vol 165 (4) ◽  
pp. 1188-1194 ◽  
Author(s):  
Y Citri ◽  
J Braun ◽  
D Baltimore
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
B Lymphocyte ◽  
Malignant Cell ◽  
Lymphoid Cells ◽  
Growth Property ◽  
B Lymphoid ◽  
A Minor

Recently, a minor subpopulation of murine B lymphocytes, Ly-1+ B cells, has been distinguished by its unique ontogeny, tissue distribution, and prominence in certain autoimmune and neoplastic B cell diseases. We have previously described a simple murine spleen culture system that results in the spontaneous and exclusive outgrowth of long-term Ly-1+ B cell lines (B Ly-1 cells). Here, we report that the immortal growth property of B Ly-1 cells correlates with a 10-45-fold elevation of steady-state myc RNA and 2-10-fold amplification of the c-myc locus. While c-myc amplification has been observed in malignant cell lines derived from several tissues of origin, its occurrence in lymphoid cells has not been previously reported. The consistent c-myc amplification in B Ly-1 cells may reflect a unique state of this locus in the Ly-1+ B lymphocyte lineage, and contribute to the spontaneous immortalization of this B cell population in vitro, and its apparent predilection for malignant transformation in vivo.

Hyperexpression of interleukin-7 is not necessary or sufficient for transformation of a pre-B lymphoid cell line

1991 ◽  
Vol 11 (2) ◽  
pp. 854-863
Author(s):  
J C Young ◽  
M L Gishizky ◽  
O N Witte
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Protein Tyrosine Kinase ◽  
B Lymphocyte ◽  
Growth Stimulation ◽  
Malignant Phenotype ◽  
Interleukin 7 ◽  
B Lymphoid

Interleukin-7 (IL-7) is a potent stimulator of pre-B-lymphocyte proliferation. Pre-B cells transformed by a variety of oncogenes including those of the ABL protein tyrosine kinase family were screened for endogenous IL-7 mRNA expression by polymerase chain reaction and a sensitive bioassay for secreted IL-7. Some v-abl but none of the BCR/ABL, v-src, v-fms, v-myc, v-ras, or v-raf transformants analyzed contained elevated IL-7 transcripts. None of the cell lines secreted detectable bioactivity. We overexpressed IL-7 via a retroviral vector in an IL-7-dependent pre-B cell line to assess the potential for autocrine growth stimulation and malignant transformation. We achieved dramatic deregulation of IL-7 translational suppression by removing portions of the 5' flanking region. Levels of IL-7 expression much greater than those needed to establish factor-independent growth did not induce colony formation in agar by IL-7-expressing pre-B cell lines, and the majority of these lines were nontumorigenic in syngeneic mice. The same pre-B cell line transformed by v-abl displayed a highly malignant phenotype while containing dramatically lower IL-7 transcript levels. We conclude that endogenous IL-7 expression is not a necessary event in transformation of pre-B cells, nor is it sufficient to explain the malignant phenotype in v-abl-transformed cells. Up regulation of endogenous IL-7 expression in some transformed pre-B cells may be one of several synergistic events which can lead to malignant conversion.

scholarly journals Circulating clonotypic B cells in classic Hodgkin lymphoma

Blood ◽  
2009 ◽  
Vol 113 (23) ◽  
pp. 5920-5926 ◽  
Author(s):  
Richard J. Jones ◽  
Christopher D. Gocke ◽  
Yvette L. Kasamon ◽  
Carole B. Miller ◽  
Brandy Perkins ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cell Lines ◽  
Small Population ◽  
Lymphoid Cells ◽  
Stem Cell Marker ◽  
Proliferative Potential ◽  
Immunoglobulin Gene ◽  
B Lymphoid

Abstract Although Hodgkin and Reed-Sternberg (HRS) cells are B lymphoid cells, they are unlike any normal cells of that lineage. Moreover, the limited proliferative potential of HRS cells belies the clinical aggressiveness of Hodgkin lymphoma (HL). More than 20 years ago, the L428 HL cell line was reported to contain a small population of phenotypic B cells that appeared responsible for the continued generation of HRS cells. This observation, however, has never been corroborated, and such clonotypic B cells have never been documented in HL patients. We found that both the L428 and KM-H2 HL cell lines contained rare B-cell subpopulations responsible for the generation and maintenance of the predominant HRS cell population. The B cells within the HL cell lines expressed immunoglobulin light chain, the memory B-cell antigen CD27, and the stem cell marker aldehyde dehydrogenase (ALDH). Clonal CD27+ALDHhigh B cells, sharing immunoglobulin gene rearrangements with lymph node HRS cells, were also detected in the blood of most newly diagnosed HL patients regardless of stage. Although the clinical significance of circulating clonotypic B cells in HL remains unclear, these data suggest they may be the initiating cells for HL.

scholarly journals Hyperexpression of interleukin-7 is not necessary or sufficient for transformation of a pre-B lymphoid cell line.

1991 ◽  
Vol 11 (2) ◽  
pp. 854-863 ◽  
Author(s):  
J C Young ◽  
M L Gishizky ◽  
O N Witte
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Protein Tyrosine Kinase ◽  
B Lymphocyte ◽  
Growth Stimulation ◽  
Malignant Phenotype ◽  
Interleukin 7 ◽  
B Lymphoid

Interleukin-7 (IL-7) is a potent stimulator of pre-B-lymphocyte proliferation. Pre-B cells transformed by a variety of oncogenes including those of the ABL protein tyrosine kinase family were screened for endogenous IL-7 mRNA expression by polymerase chain reaction and a sensitive bioassay for secreted IL-7. Some v-abl but none of the BCR/ABL, v-src, v-fms, v-myc, v-ras, or v-raf transformants analyzed contained elevated IL-7 transcripts. None of the cell lines secreted detectable bioactivity. We overexpressed IL-7 via a retroviral vector in an IL-7-dependent pre-B cell line to assess the potential for autocrine growth stimulation and malignant transformation. We achieved dramatic deregulation of IL-7 translational suppression by removing portions of the 5' flanking region. Levels of IL-7 expression much greater than those needed to establish factor-independent growth did not induce colony formation in agar by IL-7-expressing pre-B cell lines, and the majority of these lines were nontumorigenic in syngeneic mice. The same pre-B cell line transformed by v-abl displayed a highly malignant phenotype while containing dramatically lower IL-7 transcript levels. We conclude that endogenous IL-7 expression is not a necessary event in transformation of pre-B cells, nor is it sufficient to explain the malignant phenotype in v-abl-transformed cells. Up regulation of endogenous IL-7 expression in some transformed pre-B cells may be one of several synergistic events which can lead to malignant conversion.

scholarly journals Clonal diversity in the B cell repertoire of patients with X-linked agammaglobulinemia.

1989 ◽  
Vol 169 (6) ◽  
pp. 2109-2119 ◽  
Author(s):  
R Anker ◽  
M E Conley ◽  
B A Pollok
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Clonal Diversity ◽  
Chain Gene ◽  
Gene Rearrangements ◽  
B Cell Differentiation ◽  
Cell Repertoire ◽  
Lymphoid Lineage ◽  
B Cell Repertoire ◽  
B Lymphoid

Ig protein and mRNA expression was examined in a collection of 18 monoclonal EBV-transformed B cell lines derived from five patients with X-linked agammaglobulinemia (XLA). A diversity of H and L chain isotypes were synthesized by these lines: the majority (12 lines) expressed mu kappa chains, while mu lambda (two lines), gamma kappa (one), gamma lambda (one), delta lambda (one), and alpha kappa (one) isotype expression was also observed. For all the mu kappa-producing XLA B cell lines, the mu and kappa mRNA transcripts were of native size, and sequence analysis across the regions of VHDJH and V kappa J kappa gene joining showed that Ig gene rearrangements occurred in a typical manner. A variety of VHDJH and V kappa J kappa gene rearrangements were observed, not only within the set of mu kappa+ XLA B cells as a whole, but also among the cell lines derived from single patients. Southern blot analysis for genomic Ig H chain gene rearrangements was done to fully assess the extent of clonal heterogeneity among multiple mu kappa+ XLA B cell lines derived from two patients; all the B cell lines possessed distinct gene rearrangement patterns demonstrating their clonal unrelatedness. Our findings indicate that the B cell repertoire in individual XLA patients is clonally diverse and that it is unlikely that the defect in B cell differentiation in XLA is the result of inefficient or ineffective rearrangement of Ig H or L chain genes. Rather, this study provides support for the idea that the XLA defect relates to a more generalized cellular function, such as regulating the proliferation and/or clonal expansion of cells of the B lymphoid lineage.

Accessibility of the promoter sequence in the J-chain gene is regulated by chromatin changes during B-cell differentiation

1986 ◽  
Vol 6 (11) ◽  
pp. 4031-4038
Author(s):  
M E Minie ◽  
M E Koshland
Keyword(s):  
B Cell ◽  
Early Stage ◽  
Promoter Sequence ◽  
Immunoglobulin M ◽  
Chain Gene ◽  
B Cell Differentiation ◽  
Cell Stage ◽  
J Chain ◽  
Lymphoid Lines ◽  
Nuclease Digestion

The gene for the immunoglobulin M (IgM)-polymerizing protein, the J chain, is activated when the mature B cell is triggered to secrete pentamer IgM. Activation of the gene was found to be associated with chromatin changes in a 240-base-pair region at the 5' end of the gene. Analyses of lymphoid lines showed that the 5' region was resistant to nuclease digestion at the immature B-cell stage; it became slightly more accessible in mature B cells and cells at an early stage in the IgM response and then displayed an open, hypersensitive structure in IgM-secreting cells. In addition, analyses of normal, mitogen-stimulated lymphocytes showed that the open hypersensitive structure was coinducible with J-chain gene expression. These results suggest that the 5' chromatin changes precede transcription, making control sequences within the site accessible to regulatory factors.

Lymphoid and other tissue-specific phenotypes of polyomavirus enhancer recombinants: positive and negative combinational effects on enhancer specificity and activity

1986 ◽  
Vol 6 (6) ◽  
pp. 2068-2079
Author(s):  
B A Campbell ◽  
L P Villarreal
Keyword(s):  
Cell Lines ◽  
Heavy Chain ◽  
Murine Leukemia Virus ◽  
Tissue Specificity ◽  
Leukemia Virus ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Lymphoid Cells ◽  
B Lymphoid ◽  
Murine Leukemia

Heterologous enhancer recombinants and deletions of the polyomavirus (Py) noncoding region were constructed and analyzed for tissue specificity of DNA replication and transcription in a number of lymphoid and other cell lines. The simian virus 40 72-base-pair repeat, mouse immunoglobulin heavy-chain enhancer, and Moloney murine leukemia virus enhancer were inserted into the PvuII-D locus (nucleotides 5128 through 5265) of Py. The ability of these recombinants and the parental PvuII-D deletion mutant to replicate in permissive 3T6 cells and MOP-6 cells as well as in nonpermissive mouse B lymphoid, T lymphoid, mastocyte, and embryonal carcinoma cells was determined. Wild-type Py DNA was not permissive for replication in most lymphoid cell lines, except one hybridoma line. Simply deleting the Py PvuII-D region, however, gave Py an expanded host range, allowing high-level replication in some T lymphoid and mastocytoma cell lines, indicating that this element can be a tissue-specific negative as well as positive element. Substitution of the murine leukemia virus enhancer for Py PvuII-D yielded a Py genome which retained the ability to replicate in 3T6 cells but also replicated well in B lymphoid cells. Substitution with the immunoglobulin heavy-chain enhancer allowed replication in B lymphoid cells but interfered with replication in 3T6 cells and mastocytomas. Surprisingly, substitution with the simian virus 40 72-base-pair enhancer repeat gave a recombinant which would not replicate in any cell line tried, including MOP-6 cells, even though other recombinants with this enhancer would replicate. Thus, we observed both cooperation and interference in these combinations between enhancer components and the Py genome and that these combined activities were cell specific. These results are presented as evidence that there may be a positional dependence, or syntax, for the recognition of genetic elements controlling Py tissue specificity.

Rearrangement and diversification of immunoglobulin light-chain genes in lymphoid cells transformed by reticuloendotheliosis virus

1989 ◽  
Vol 9 (11) ◽  
pp. 4970-4976
Author(s):  
J Y Zhang ◽  
W Bargmann ◽  
H R Bose
Keyword(s):  
Cell Lines ◽  
Light Chain ◽  
Lymphoid Cells ◽  
Chain Gene ◽  
Gene Rearrangements ◽  
B Cell Differentiation ◽  
Immunoglobulin Light Chain ◽  
Light Chain Gene ◽  
Transformed Cell Lines

Avian lymphoid cells transformed by reticuloendotheliosis virus (REV-T) serve as a model to analyze the mechanism by which B-cell differentiation and antibody diversification occur in birds. Immunoglobulin light-chain gene rearrangements, diversification, and expression were analyzed in 72 independently derived REV-T-transformed cell lines. Lymphoid cells transformed as the result of expression of the v-rel oncogene were divided into two distinct groups based on light-chain gene rearrangements. The status of the light-chain gene loci in these REV-T-transformed cell lines was determined in part by the ages of the chickens whose spleen cells were transformed. In embryonic spleen cell lines transformed by the v-rel oncogene, rearrangements were not detected, even after prolonged culture in vitro, indicating that these cells are arrested in B-cell differentiation. REV-T transformants derived from spleens obtained from chickens 2 weeks old or older, however, had at least one light-chain allele rearranged. All of the cell lines analyzed which exhibited rearranged light-chain genes contained light-chain transcripts, and most of the REV-T-transformed cells which displayed light-chain rearrangements expressed immunoglobulin protein. REV-T, therefore, transforms B-lymphoid cells at phenotypically different stages of development. Many REV-T-transformed cells undergo immunoglobulin chain gene rearrangements during prolonged propagation in vitro. Most of the cell lines which rearrange their light-chain alleles also undergo diversification during cultivation in vitro. Light-chain diversification occurs during or after the rearrangement event.

scholarly journals Emergence of a B-cell lymphoblastic lymphoma in a patient with B-cell chronic lymphocytic leukemia: evidence for the single-cell origin of the two tumors

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 797-804
Author(s):  
V Pistoia ◽  
S Roncella ◽  
PF Di Celle ◽  
M Sessarego ◽  
G Cutrona ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Lines ◽  
Peripheral Blood ◽  
Chromosomal Abnormalities ◽  
Cell Clone ◽  
Lymphoblastic Lymphoma ◽  
Lymphocytic Leukemia ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Chain Gene

A patient is described who presented with a chronic lymphocytic leukemia (CLL) and later developed a lymphoblastic lymphoma. The cells from the CLL were typical mature B lymphocytes as could be assessed by morphologic, cytochemical, and surface marker analyses. The cells from the lymphoblastic lymphoma were immature B cells that expressed CD10, CD20, and HLA-DR markers, but not surface Ig or cytoplasmic mu chains, and were negative for terminal deoxynucleotidyl transferase (TdT). The cells of two continuous cell lines, obtained from the bone marrow and the peripheral blood of the patient, had the same phenotype as the lymphoblastic lymphoma cells, did not contain the Epstein-Barr virus genome, and displayed malignant features in vitro, including the capacity to form colonies in agar. The two cell lines also shared identical chromosomal abnormalities, a finding which suggests that they derived from the same malignant cell already present in vivo. Such chromosomal abnormalities were not seen in the karyotype of the peripheral blood cells at the onset of the disease. Analysis of the Ig heavy chain genes using a DJ-specific probe showed the very same monoclonal rearrangement in the cells from the B-CLL, the lymphoblastic lymphoma and the two cell lines, thus demonstrating their common clonal origin. By contrast, a monoclonal rearrangement of the lambda chain gene locus was found in the B-CLL cells only, a finding consistent with their exclusive capacity to express surface IgM lambda. This patient represents a rare case in whom a chronic lymphoproliferative disorder with mature malignant cells transforms into a lymphoblastic lymphoma characterized by cells frozen at a very early maturational stage. The possible mechanisms leading to such transformation within the same cell clone are discussed.

scholarly journals Monoclonal antibodies to the 140,000 mol wt glycoprotein of B lymphocyte membranes (CR2 receptor) initiates proliferation of B cells in vitro

Blood ◽  
1985 ◽  
Vol 66 (4) ◽  
pp. 824-829
Author(s):  
BS Wilson ◽  
JL Platt ◽  
NE Kay
Keyword(s):  
Monoclonal Antibodies ◽  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
B Lymphocyte ◽  
Human Peripheral Blood ◽  
Raji Cell ◽  
Lymphoid Cells ◽  
Humoral Immune

Several mouse monoclonal IgG antibodies (AB1, AB2, AB3, and AB5) were developed that reacted with a 140,000 mol wt glycoprotein on the surface of cultured RAJI B lymphoid cells. The antibodies reacted with purified normal human peripheral blood B cells and CLL Ig+ B cells and showed specific germinal center and mantle zone staining in tissue sections of secondary lymphoid organs. Immunodepletion studies using 125I surface-labeled Raji cell membrane antigens demonstrated that the antigen identified by AB5 is the same 140,000 mol wt glycoprotein detected by anti-B2 that has recently been shown to react with the C3d fragment or CR2 receptor. (Iida et al: J Exp Med 158:1021, 1983). Addition of the AB series and anti-B2 monoclonal antibodies to cultures of purified human peripheral blood B cells resulted in the uptake of 3H- thymidine at two to six times background control levels provided that irradiated autologous T cells were added to the culture. Stimulation was not evoked by other monoclonal antibodies to B cell surface molecules (ie, B1, BA-1, BA-2, and HLA-DR). Pepsin-generated F(ab')2 fragments of anti-CR2 antibodies were essentially as effective as the intact IgG molecule in stimulating B cells. Induction of B cell proliferation by antibody binding to CR2 suggests that the C3d receptor may have an integral role in regulation of humoral immune response.

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