scholarly journals Delay of Early B-Lymphocyte Development by Gamma 2b Immunoglobulin Transgene: Effect on Differentiation-Specific Molecules

1990 ◽  
Vol 1 (2) ◽  
pp. 105-112 ◽  
Author(s):  
Kathleen A. Denis ◽  
Scott Provost ◽  
Owen N. Witte ◽  
Ralph L. Brinster ◽  
Ursula Storb

Mice transgenic forγ2b Ig heavy chain were examined for alterations in B-cell differentiation and endogenous Ig gene rearrangement and expression. Fresh bone marrow from these mice was markedly reduced in BP-1+cells and there were small reductions in B220+and sIg+cells. A-MuLV (Abelson murine leukemia virus) transformants from these bone marrow cells showed little alteration in Ig gene rearrangement and expression when compared to controls, however. Isolation of the B-lymphoid compartment from these mice in vitro using LBMC (lymphoid bone marrow cultures) enabled more detailed characterization of the effects of the transgene. LBMC derived fromγ2b transgenic mice had similar growth kinetics, but a 4-5-week delay in the expression of endogenous mu Ig in comparison to control cultures. Nucleic acids derived from these early cultures prior to endogenous mu Ig expression showed reduced Ig JHrearrangements, some sterile mu transcription, low levels of BP-1 expression, and virtually undetectable TdT (terminal deoxynucleotidyl transferase) expression. Thus, thisγ2b transgene appears able to affect early B-lymphocyte development.

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1316-1324 ◽  
Author(s):  
MR Loken ◽  
VO Shah ◽  
KL Dattilio ◽  
CI Civin

Abstract A panel of B lymphoid-reactive monoclonal antibodies was used to analyze the phenotypic changes that accompany B lymphocyte development in normal human bone marrow. The B lymphoid cells were identified using light scattering and the expression of CD19 on a flow cytometer. Quantitative three-color immunofluorescence was then used to correlate other cell surface antigens on these cells identified as B lymphoid in normal marrow. CD10 and CD20 identified almost exclusive populations and provided a convenient means of discriminating between the less and more mature B lineage cells. The CD10+ cells could be further subdivided using CD34. The population of CD19+, CD10+, CD34+ cells comprised only 0.6% of marrow cells, but these contained the majority of terminal deoxynucleotidyl transferase (TdT+) cells. In the assessment of class II antigens, HLA-DR was expressed on all B lineage cells whereas HLA-DP preceded HLA-DQ in appearance during the developmental process. Among the later antigens expressed on B lineage cells, cell surface IgM, CD20, and HLA-DQ were expressed at essentially the same time. Cell surface CD10 was lost at the time when CD21 and CD22 were acquired on the cell surface. These data illustrate that multiparameter flow cytometry can be used to define a continuous progression of stages of B lymphocyte development based on cell surface antigen expression even though these cells represent a minor fraction of normal marrow cells.


Blood ◽  
2002 ◽  
Vol 99 (6) ◽  
pp. 2154-2161 ◽  
Author(s):  
Francisco Medina ◽  
Carmen Segundo ◽  
Antonio Campos-Caro ◽  
Inés González-Garcı́a ◽  
José A. Brieva

Abstract Plasma cells (PCs) are the final B-cell differentiation stage. Recent evidence reveals relevant functional differences within the PC compartment. In rodents, early PCs formed in secondary lymphoid tissues show enhanced apoptosis and short life span, whereas PCs present in a final destination organ, such as the bone marrow (BM), have reached a stable prolonged survival state. BM PCs arrive at this organ as a circulating precursor whose cellular nature remains uncertain. An initial aim of this study was to characterize this circulating cell. We hypothesized that antibody-secreting cells detectable in the human blood after immunization might be a candidate precursor. These cells were obtained from the blood of volunteers immunized 6 days earlier with tetanus toxoid (tet), and they were unambiguously identified as PCs, as demonstrated by their expression of the CD38h phenotype, by morphology, by immunoglobulin (Ig) intracytoplasmic staining, and by IgG-tet–secreting capacity in vitro. In addition, by using the common CD38h feature, human PCs from tonsil (as a possible source of early PCs), from blood from tet-immunized donors (as the putative precursors of BM PCs), and from BM (as a deposit organ) have been purified and their phenotypes compared. The results show that a variety of differentiation molecules, proteins involved in the control of apoptosis, the B-cell transcription factors, positive regulatory domain I-binding factor 1/B lymphocyte-induced maturation protein 1 and B cell–specific activating protein and, at least partially, the chemokine receptor CXCR4 were expressed by human PCs following a gradient of increasing maturity in the direction: tonsil→blood→BM. However, PCs from these different organs showed a local pattern of adhesion molecule expression. These observations are discussed in light of the complex physiology of the human PC compartment.


Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 193-199
Author(s):  
JM Heard ◽  
B Sola ◽  
MA Martial ◽  
S Fichelson ◽  
S Gisselbrecht

The replication-competent Friend leukemia virus (F-MuLV) induces leukemias involving three hematopoietic lineages after a latent period of several months. In an attempt to elucidate the early events of the leukemogenic process, we looked for a method allowing the isolation and the long term in vitro maintenance of preleukemic cells. When established as long-term cultures according to the technique described by Dexter et al, bone marrow cells obtained from 7/7 apparently healthy F-MuLV-infected preleukemic mice led to the accumulation of immature myeloblastic cells, and to the generation of permanent myeloblastic cell lines, which in most cases further became tumorigenic in preirradiated recipient animals. The delays required to obtain cell lines were shorter when the duration of the in vivo infection was longer, suggesting that these cells were committed into the leukemogenic pathway before their transfer into culture flasks. The myelomonocytic preleukemic cells exhibited normal sensitivity to purified preparations of CSFs, but acquired the capacity to grow in the absence of exogenous CSF stimulation. Examination of integrated provirus copies demonstrated that the preleukemic cell proliferation involved a single or a few clones which may progress in vitro from a preleukemic to a fully malignant stage without major modifications of the integrated provirus copies.


1994 ◽  
Vol 137 (1) ◽  
pp. 185-201 ◽  
Author(s):  
Antonius Rolink ◽  
Hajime Karasuyama ◽  
Dirk Haasner ◽  
Ulf Grawunder ◽  
Inga-Lill Martensson ◽  
...  

1995 ◽  
Vol 165 (1) ◽  
pp. 44-54 ◽  
Author(s):  
Jeff D. Hardin ◽  
Sharon Boast ◽  
Pamela L. Schwartzberg ◽  
Grace Lee ◽  
Fred W. Alt ◽  
...  

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 251.2-251
Author(s):  
J. Thiel ◽  
K. Fischer ◽  
R.E. Voll ◽  
R. Lorenzetti ◽  
B. Bannert ◽  
...  

1978 ◽  
Vol 147 (3) ◽  
pp. 708-718 ◽  
Author(s):  
N H Pazmiño ◽  
J N Ihle ◽  
A L Goldstein

Terminal deoxynucleotidyl transferase (TdT) expression in bovine serum albumin (BSA) gradient-fractionated bone marrow cells was examined in NIH Swiss nu/nu and thymectomized C57BL/6 mice. In nude mice, TdT levels were approximately 10% of those of thymus-bearing littermates. In C57BL/6 mice, thymectomy caused a time-dependent loss of TdT activity in bone marrow cells. To determine whether or not not the apparent thymic requirement for TdT expression in bone marrow was mediated by thymic hormones, we examined the effects of thymosin fraction 5. Treatment of either NIH Swiss nu/nu or thymectomized C57BL/6 mice with thymosin fraction 5 restored the levels of TdT activity in BSA gradient-fractionated bone marrow cells to normal. Moreover, treatment of BSA gradient-fractionated bone marrow cells from NIH Swiss nu/nu or thymectomized C57BL/6 mice in tissue culture with thymosin fraction 5 induced TdT expression. In tissue culture, TdT induction was optimal with 25 ng/ml of thymosin fraction 5, it occurred within 6 h, and it was completely inhibited by actinomycin D. The effect was specific in that neither control nor spleen fraction 5-treated cells were induced to express TdT. These data demonstrate that TdT expression in bone marrow cells is under the direct control of thymic polypeptide hormones.


Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1316-1324 ◽  
Author(s):  
MR Loken ◽  
VO Shah ◽  
KL Dattilio ◽  
CI Civin

A panel of B lymphoid-reactive monoclonal antibodies was used to analyze the phenotypic changes that accompany B lymphocyte development in normal human bone marrow. The B lymphoid cells were identified using light scattering and the expression of CD19 on a flow cytometer. Quantitative three-color immunofluorescence was then used to correlate other cell surface antigens on these cells identified as B lymphoid in normal marrow. CD10 and CD20 identified almost exclusive populations and provided a convenient means of discriminating between the less and more mature B lineage cells. The CD10+ cells could be further subdivided using CD34. The population of CD19+, CD10+, CD34+ cells comprised only 0.6% of marrow cells, but these contained the majority of terminal deoxynucleotidyl transferase (TdT+) cells. In the assessment of class II antigens, HLA-DR was expressed on all B lineage cells whereas HLA-DP preceded HLA-DQ in appearance during the developmental process. Among the later antigens expressed on B lineage cells, cell surface IgM, CD20, and HLA-DQ were expressed at essentially the same time. Cell surface CD10 was lost at the time when CD21 and CD22 were acquired on the cell surface. These data illustrate that multiparameter flow cytometry can be used to define a continuous progression of stages of B lymphocyte development based on cell surface antigen expression even though these cells represent a minor fraction of normal marrow cells.


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