Proliferation of B Cell Precursors in Bone Marrow of Pristane-Conditioned and Malaria-Infected Mice: Implications for B Cell Oncogenesis

Osmond, Dennis G.; Priddle, S.; Rico-Vargas, S.

doi:10.1007/978-3-642-75889-8_19

Cited by 12 publications

(9 citation statements)

References 21 publications

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“…In the adult mouse, 3-5 x 107 newly formed B cells are generated per day in the bone marrow (BM) by proliferation and differentiation of early B cell progenitors (Osmond, 1990;Osmond et al, 1990). During maturation, pro-B and pre-B cells undergo an ordered sequence of immunoglobulin heavy (IgH) and light (IgL) chain gene rearrangements and the loss or acquisition of several lineage-related molecules (Tonegawa, 1983;Forster et al, 1989;Hardy et al, 1991;Rolink and Melchers, 1991;Ehlich et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

“…During maturation, pro-B and pre-B cells undergo an ordered sequence of immunoglobulin heavy (IgH) and light (IgL) chain gene rearrangements and the loss or acquisition of several lineage-related molecules (Tonegawa, 1983;Forster et al, 1989;Hardy et al, 1991;Rolink and Melchers, 1991;Ehlich et al, 1993). Despite the large number of B cell precursors generated, only 2-3 x 106 IgM+IgD+ mature B cells enter the bloodstream and are incorporated into the peripheral pool (Forster et al, 1989;Osmond, 1990;Osmond et al, 1990). Further maturation of IgM+IgDimmature B cells results in the co-expression of surface IgM Oxford University Press and IgD which defines the mature B cell population.…”

Section: Introductionmentioning

confidence: 99%

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Developmental regulation of the Bcl-2 protein and susceptibility to cell death in B lymphocytes.

et al. 1994

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Cell death is a prominent feature of B cell development. For example, a large population of B cells dies at the pre‐B cell stage presumably due to the failure to express a functional immunoglobulin receptor. In addition, developing B cells expressing antigen receptors for self are selectively eliminated at the immature B cell stage. The molecular signals that control B cell survival are largely unknown. The product of the bcl‐2 proto‐oncogene may be involved as its overexpression inhibits apoptotic cell death in a variety of biological systems. However, the physiological role of the endogenous Bcl‐2 protein during B cell development is undetermined. Here we show a striking developmental regulation of the Bcl‐2 protein in B lymphocytes. Bcl‐2 is highly expressed in CD43+ B cell precursors (pro‐B cells) and mature B cells but downregulated at the pre‐B and immature B cell stages of development. We found that Bcl‐2 expressed by B cells is a long‐lived protein with a half‐life of approximately 10 h. Importantly, susceptibility to apoptosis mediated by the glucocorticoid hormone dexamethasone is stage‐dependent in developing B cells and correlates with the levels of Bcl‐2 protein. Furthermore, expression of a bcl‐2 transgene rescued pre‐B and immature B cells from dexamethasone‐induced cell death, indicating that Bcl‐2 can inhibit the apoptotic cell death of progenitors and early B cells. Taken together, these findings argue that Bcl‐2 is a physiological signal controlling cell death during B cell development.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Developmental regulation of the Bcl-2 protein and susceptibility to cell death in B lymphocytes.

et al. 1994

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“…N 'aturally occurring cell death is common during B cell maturation and is accomplished by apoptosis, a morphologically defined process that is widespread during embryogenesis and postnatal development (1). During B lymphocyte differentiation, it is estimated that as few as one tenth of the daily 3-5 • 107 newly formed B cells is incorporated into the peripheral mature pool (2,3). Death appears to be the fate of most B cell precursors with the majority of the cell loss occurring during the transition from large, cytoplasmic ~ chain-producing B cell precursors to small pre-B cells (4,5).…”

mentioning

confidence: 99%

bcl-x exhibits regulated expression during B cell development and activation and modulates lymphocyte survival in transgenic mice.

Grillot

Merino

Pena

et al. 1996

The Journal of Experimental Medicine

170

111

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SummaryWe have assessed during B cell development, the regulation and function of bcl-x, a member of the bcl-2 family of apoptosis regulatory genes. Here we show that Bcl-xr, a product of bd-x, is expressed in pre-B cells but downregulated at the immature and mature stages of B cell development. Bcl-xr but not Bcl-2 is rapidly induced in peripheral B cells upon surface immunoglobulin M (IgM) cross-linking, CD40 signaling, or LPS stimulation. Transgenic mice that overexpressed Bcl-xt within the B cell lineage exhibited marked accumulation of peripheral B cells in lymphoid organs and enhanced survival of developing and mature B cells. B cell survival was further increased by simultaneous expression of bcl-xL and bcl-2 transgenes. These studies demonstrate that Bcl-2 and Bcl-x t are regulated differentially during B cell development and activation of mature B cells. Induction of Bcl-XL after signaling through surface IgM and CD40 appears to provide mature B cells with an additional protective mechanism against apoptotic signals associated with antigen-induced activation and proliferation.

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“…Depletion of mature B cells with antibodies does not influence the kinetics of B cell formation and this has been interpreted to mean that there is no feedback from the pool of peripheral cells (3). The process is certainly influenced by chronic antigen exposure, injections of polyclonal IgG, graft-vs.-host disease, malaria, age, and cyclic neutropenia (4)(5)(6)(7)(8). However, little information is available about mechanisms involved in those phenomena or what controls movement of the site of B lymphopoiesis from liver and spleen to bone marrow during late embryonic life (1).…”

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confidence: 99%

Suppression of B lymphopoiesis during normal pregnancy.

Medina

Smithson

Kincade

1993

The Journal of Experimental Medicine

217

132

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SummaryWe describe a dramatic reduction in numbers and activity of committed B lymphocyte precursors in the bone marrow of normal pregnant mice. Changes in cells responsive to were evident as early as 6.5 d of pregnancy and values were <10% of normal at parturition. B lineage precursors, identified by display of CD45R and absence of surface IgM, were also substantially depressed, and subpopulations representing different stages in the B lineage were assessed by three-color flow cytometry. Early pro-B ceUs are medium to large in size and have been previously characterized by low expression of the heat-stable antigen (HSA). This category of cells was not reduced, and in fact may have been slightly elevated, during pregnancy. In contrast, all subsequent populations of B lineage precursors, defined by patterns of expression of heat-stable and CD43 antigens, were substantially depressed. The immediate precursors of B cells (small pre-B cells) were identified by small size, expression of CD45R, absence of CD43, and lack of surface IgM. These were the most reduced of any phenotypically defined population in bone marrow. Numbers of newly formed B ceUs, characterized by the presence of sIgM, but not slgD, were also diminished. However, B cells with a mature phenotype (slgM + , slgD +) were present in normal to somewhat devated numbers. Mitogen-responsive B cells donable in a semisolid agar assay were not significantly affected. A bromodeoxyuridine (BrdU) labeling technique was used to evaluate mitotic activity, which revealed an increased proportion of long-lived lymphocytes in the bone marrow of pregnant mice_ These observations indicate that B lymphopoiesis is markedly downregulated during pregnancy and that all precursor populations beyond the early pro-B cell stage are affected. The pregnancyrelated changes in bone marrow were selective for B lineage precursors, as cells expressing myeloid and erythroid markers were not reduced. In spleen, evidence was obtained for partial depletion of one subset of B cells. These cells, which have been reported to be recent immigrants from marrow, are characterized as having high levels of sIgM and HSA. Changes in other major B lymphocyte subsets in the spleen were less remarkable. When considered with results from the BrdU labeling procedure, the findings indicate that both production and export of lymphocytes from marrow may be substantially decreased. Numbers of B cell precursors were higher in postpartum animals whose litters wereremoved at birth, suggesting that lactation may prolong regeneration of lymphocyte production. We also found that acute estrogen treatment selectively reduced numbers of B lymphocyte precursors in bone marrow. These observations raise the interesting possibility that endocrine mechanisms involving sex steroids may be important for normal regulation of B lymphopoiesis.

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Proliferation of B Cell Precursors in Bone Marrow of Pristane-Conditioned and Malaria-Infected Mice: Implications for B Cell Oncogenesis

Cited by 12 publications

References 21 publications

Developmental regulation of the Bcl-2 protein and susceptibility to cell death in B lymphocytes.

Developmental regulation of the Bcl-2 protein and susceptibility to cell death in B lymphocytes.

bcl-x exhibits regulated expression during B cell development and activation and modulates lymphocyte survival in transgenic mice.

Suppression of B lymphopoiesis during normal pregnancy.

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