Pre‐B cells in bone marrow: peanut agglutinin binding and separation of cytoplasmic μ chain‐bearing cell populations in normal, post‐irradiation and polycythemic mice using fluorescence‐activated cell sorting

Osmond, Dennis G.

doi:10.1002/eji.1830140604

Cited by 9 publications

(5 citation statements)

References 23 publications

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“…Many c/z+s//-pre-B cells (75%) are actually small post-mitotic cells that mature into sIgM+ cells without further division. The small c/i+s/z" cells lie within the population of sIgM-small lymphocytes (Opstelten & Osmond, 1983, Landreth et al 1981, Osmond 1984, already noted as turning over rapidly. From radioautographic data of the 'H-thymidine labeling of small c/i+sp-pre-B cells a turnover of approximately 3%/h may be calculated (Landreth et al 1981).…”

Section: B Lymphocyte Production In Bone Marrowmentioning

confidence: 95%

Population Dynamics of Bone Marrow B Lymphocytes

Osmond

1986

Immunological Reviews

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193

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The dynamic concepts of lymphocyte populations which heralded the era of modern cellular immunobiology have been generally substantiated by recent studies and are still being correlated with functional properties. B lineage cells in the bone marrow are dynamically heterogeneous: A large majority are newly-formed, rapidly renewed cells, continuously produced from precursor cells within the bone marrow and disseminated during a terminal maturation phase via the blood stream. These cells develop low densities of sIgM in the extravascular bone marrow parenchyma and may undergo some further maturation within bone marrow sinusoids. The rate of production of bone marrow B cells appears to depend partly on the total load of exogenous agents to which the individual is exposed. Bone marrow lymphocyte production maintains a population of rapidly renewed virgin B cells in the peripheral lymphoid tissues. A small proportion of these cells apparently may be selected to enter a long-lived pool of B cells if suitably activated. By continuously creating novel clonotypes this process potentially can anticipate new antigen challenges and allow the immune system to build up a repertoire of antigen specificities most appropriate to the individual's changing environment throughout life. A minority of B lymphocytes in the bone marrow comprises slowly renewed, long-lived cells which enter and leave the bone marrow parenchyma as a selective part of the recirculating lymphocyte pool in the blood stream. Their role in the bone marrow is unknown. They include antigen-specific B memory cells, yet these are not activated within the bone marrow itself. No regulatory role has yet been directly demonstrated. Recently activated B cells enter from the spleen after secondary antigenic stimulation to develop into antibody-producing cells within the bone marrow. In assessing the significance of any phenotypically or functionally distinct B cell subset in the bone marrow, a basic consideration is to assign the subset to one of the foregoing dynamic categories. Within a given category cells may represent one stage in a time sequence of development. The bone marrow also produces lymphocytes of as yet uncertain lineage and contains selected subsets of T cells. The roles of these cells in cytotoxic, regulatory, or other events remain to be elucidated.

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Section: B Lymphocyte Production In Bone Marrowmentioning

confidence: 95%

Population Dynamics of Bone Marrow B Lymphocytes

Osmond

1986

Immunological Reviews

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193

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“…All AA4 + IgM + cells were IgD lo or IgD − , CD24 ++ , CD21 − , CD23 − , in further agreement with their immature B cell stage. All IgM − cells failed to show significant TdT mRNA levels, in contrast to the tight TdT (Terminal deoxynucleotidyl Transferase) expression by the pro B cells [34], and all expressed low levels of cytoplasmic IgM and high surface PNA expression, consistent with pre-B cell stage [41]. Low cytoplasmic IgM level excluded the possibility of IgM − plasmacytoma.…”

Section: Resultsmentioning

confidence: 88%

Germline Mutations in Mtap Cooperate with Myc to Accelerate Tumorigenesis in Mice

et al. 2013

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ObjectiveThe gene encoding the methionine salvage pathway methylthioadenosine phosphorylase (MTAP) is a tumor suppressor gene that is frequently inactivated in a wide variety of human cancers. In this study, we have examined if heterozygosity for a null mutation in Mtap (MtaplacZ) could accelerate tumorigenesis development in two different mouse cancer models, Eμ-myc transgenic and Pten+/−.Methods Mtap Eμ-myc and Mtap Pten mice were generated and tumor-free survival was monitored over time. Tumors were also examined for a variety of histological and protein markers. In addition, microarray analysis was performed on the livers of MtaplacZ/+ and Mtap+/+ mice.ResultsSurvival in both models was significantly decreased in MtaplacZ/+ compared to Mtap+/+ mice. In Eµ-myc mice, Mtap mutations accelerated the formation of lymphomas from cells in the early pre-B stage, and these tumors tended to be of higher grade and have higher expression levels of ornithine decarboxylase compared to those observed in control Eµ-myc Mtap+/+ mice. Surprisingly, examination of Mtap status in lymphomas in Eµ-myc MtaplacZ/+ and Eµ-myc Mtap+/+ animals did not reveal significant differences in the frequency of loss of Mtap protein expression, despite having shorter latency times, suggesting that haploinsufficiency of Mtap may be playing a direct role in accelerating tumorigenesis. Consistent with this idea, microarray analysis on liver tissue from age and sex matched Mtap+/+ and MtaplacZ/+ animals found 363 transcripts whose expression changed at least 1.5-fold (P<0.01). Functional categorization of these genes reveals enrichments in several pathways involved in growth control and cancer.ConclusionOur findings show that germline inactivation of a single Mtap allele alters gene expression and enhances lymphomagenesis in Eµ-myc mice.

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“…They do, however, show apparent cyclical variation in number over time, indicating that their presence in blood does not arise from a static mechanism (Table 1). In a series of elegant studies (70)(71)(72)(73) …”

Section: Pre-b Cells In the Blood Of Multiple Myeloma Patientsmentioning

confidence: 99%

“…Based on the work of Osmond (71)(72)(73), it would appear that immature PNA+ HLA.DR-pre-B cells may preceed PNA-HLA.DR+ pre-B that differentiate to sIg+ PNA-HLA.DR+ B cells. If this pattern is confirmed, PBL from myeloma patients will provide a valuable source for the study of human B lymphopoiesis.…”

Section: Pre-b Cells In the Blood Of Multiple Myeloma Patientsmentioning

confidence: 99%

Analysis of immunodeficiency in multiple myeloma: Observations and hypothesis

Pilarski

Mant

Ruether

1987

Clinical Laboratory Analysis

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Patients with multiple myeloma suffer from often profound immunodeficiency that seriously compromises both longevity and quality of life. The cellular basis for the immunodeficiency is unknown and the mechanism(s) giving rise to and possibly maintaining it is also unknown. In this review, evidence defining cellular defects in the nonmalignant B and T peripheral blood lymphocyte pool is summarized and discussed in terms of possible mechanisms that could give rise to the abberrant immune phenotype characteristic of many patients. The abnormalities we have defined include a deficiency of mature B lymphocytes, presence of often large numbers of pre-B cells in the blood, arrested differentiation of B cells into immunoglobulin (Ig)-secreting cells, and abnormal progenitorlike T cells in blood. The specificity repertoire of the remaining B lymphocyte population is heavily skewed toward recognition of idiotypic and shared epitopes on the variable region of Ig, perhaps reflecting immune reaction with the monoclonal myeloma lg. This may begin as a response to tumor antigen that gradually progresses to autoimmunity. A second subset of B cells present at abnormally high frequency in myeloma patients is that of antigen-experienced memory B cells, which probably encountered antigen prior to the events leading to frank myeloma. In this instance, the high frequency reflects a decrease in aggregate numbers of B cells, although it seems likely that expansion of memory clones also occurs. This is exemplified by the set of memory B cells specific for tetanus toxoid, which are present at normal number but highly enriched frequency in myeloma PBL. Both the antitumor B cells (anti-idiotype, and anti-lg) and the memory cells specific for environmental pathogens appear to be arrested in their differentiation to 19-secretors as evidenced by the lack of serum antibody in patients. The above observations are interpreted in terms of the hypothesis that immunoregulatory events triggered by the monoclonal myeloma lg establish and maintain the immunodeficiency. We speculate that autoimmune suppressor T cells specific for conserved determinants of Ig prevent pre-B cell differentiation to slg+ B cells, and B cell terminal differentiation to Ig-secretors. If correct, this analysis could lead to therapeutic approaches for the reversal of the immunodeficiency and perhaps some degree of control over the malignant growth.

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Pre‐B cells in bone marrow: peanut agglutinin binding and separation of cytoplasmic μ chain‐bearing cell populations in normal, post‐irradiation and polycythemic mice using fluorescence‐activated cell sorting

Cited by 9 publications

References 23 publications

Population Dynamics of Bone Marrow B Lymphocytes

Population Dynamics of Bone Marrow B Lymphocytes

Germline Mutations in Mtap Cooperate with Myc to Accelerate Tumorigenesis in Mice

Analysis of immunodeficiency in multiple myeloma: Observations and hypothesis

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