Life span of small lymphocytes in the thymolymphatic tissues of normal and thymus‐deprived BALB/C mice

Røpke, Carsten; Everett, N. B.

doi:10.1002/ar.1091830108

Cited by 24 publications

(9 citation statements)

References 23 publications

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“…These data are in good agreement with the results obtained from the bone marrow-reconstituted mice in both the direct labeling and the chase experiment. The 40% labeled B cells after 4 weeks and 63% after 12 weeks of continuous BrdUrd treatment of the normal mice compare to the following values in the bone marrow-reconstituted mice: 32% labeled B cells after 4 weeks of BrdUrd treatment, 33% unlabeled B cells after a 4-week and 57% after a 13-week chase. Thus, B-cell turnover may be slightly slower in the bone marrow chimeras than in the normal mice (32 versus 40% labeled cells within 4 weeks), but the difference is minor.…”

mentioning

confidence: 59%

“…While it is known that in the bone marrow of mice roughly 10 million B cells are produced per day (1), it is still controversial to which extent these cells renew the peripheral B cell pool (consisting of 10 times as many cells) (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). By using flow cytometry for the simultaneous detection of 5-bromo-2'-deoxyuridine (BrdUrd) incorporation and cell surface marker expression, we found (13) that, in mice fed BrdUrd for 1 week, less than 20% of splenic B cells were labeled with the drug (13), in agreement with data obtained in rats (11).…”

Section: Introductionmentioning

confidence: 99%

“…The data consistently show that more than two-thirds of splenic B cells in adult (>2 months old) mice have a lifetime of several weeks or months, whereas a more rapid turnover takes place in young (4 week old) mice. Thus, the peripheral B-cell pool is only slowly renewed after it has been initially built up early in life.While it is known that in the bone marrow of mice roughly 10 million B cells are produced per day (1), it is still controversial to which extent these cells renew the peripheral B cell pool (consisting of 10 times as many cells) (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). By using flow cytometry for the simultaneous detection of 5-bromo-2'-deoxyuridine (BrdUrd) incorporation and cell surface marker expression, we found (13) that, in mice fed BrdUrd for 1 week, less than 20% of splenic B cells were labeled with the drug (13), in agreement with data obtained in rats (11).…”

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confidence: 99%

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The bulk of the peripheral B-cell pool in mice is stable and not rapidly renewed from the bone marrow.

Förster

Rajewsky

1990

Proc. Natl. Acad. Sci. U.S.A.

206

100

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We have reevaluated the in vivo lifespan of B lymphocytes based on incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine into the DNA of dividing cells. To exclude potential alterations in the turnover of B-lineage cells due to the bromodeoxyuridine incorporation, we performed pulse-chase experiments comparing the appearance and disappearance of bromodeoxyuridine-labeled cells over long periods of time. The data consistently show that more than two-thirds of splenic B cells in adult (>2 months old) mice have a lifetime of several weeks or months, whereas a more rapid turnover takes place in young (4 week old) mice. Thus, the peripheral B-cell pool is only slowly renewed after it has been initially built up early in life.While it is known that in the bone marrow of mice roughly 10 million B cells are produced per day (1), it is still controversial to which extent these cells renew the peripheral B cell pool (consisting of 10 times as many cells) (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). By using flow cytometry for the simultaneous detection of 5-bromo-2'-deoxyuridine (BrdUrd) incorporation and cell surface marker expression, we found (13) that, in mice fed BrdUrd for 1 week, less than 20% of splenic B cells were labeled with the drug (13), in agreement with data obtained in rats (11). Administration of BrdUrd in vivo, however, requires careful control for toxic effects on the animal's cells because of the potential mutagenicity of the drug (14), its potential interference with cellular differentiation processes, or both (15). In this context, a critical requirement is that the proliferative behavior of BrdUrd-labeled cells is not different from that of unlabeled cells. In the present experiments, therefore, we determined the turnover of B-lineage cells in a criss-cross fashion by either measuring the appearance of BrdUrdlabeled B cells after continuous BrdUrd treatment or by determining the loss of BrdUrd-labeled cells in mice whose lymphocytes had initially been labeled with BrdUrd. In addition, we compared B-cell turnover in young versus adult mice. MATERIALS AND METHODSMice. BALB/c and CB.20 mice were bred in our animal colony and were used at either 4 weeks or 2-4 months of age.Bone Marrow Reconstitution. CB.20 mice were irradiated with 600 rads (1 rad = 0.01 Gy) and reconstituted with BALB/c bone marrow on the following day. For this purpose, bone marrow cells were isolated from adult BALB/c donors by flushing the femur with RPMI 1640 medium containing 5% (vol/vol) fetal calf serum. The cells were washed in phosphate-buffered saline (PBS) and 5 x 106 cells per mouse were injected intravenously.BrdUrd Treatment. Mice were given drinking water containing BrdUrd (Sigma, B5002) at 1 mg/ml for the indicated periods of time. Drinking water containing BrdUrd was protected from light and exchanged every 3-4 days.Staining and Flow Cytometric Analysis. The staining procedure as well as the reagents used have been described (13). Briefly, 5 x 106 spleen or bone marrow cells were first stained on the surfa...

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mentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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The bulk of the peripheral B-cell pool in mice is stable and not rapidly renewed from the bone marrow.

Förster

Rajewsky

1990

Proc. Natl. Acad. Sci. U.S.A.

206

100

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“…We are presently evaluating whether S phase BrdUrd-spleen cells accumulate in the early S phase of the cell cycle. [20,23,26, 271 which label cells exclusively through the salvage pathway and lead to estimates of the fraction of short-lived lymphocytes which are, in most cases, 2-3-fold lower than estimates based on studies using HU-treated and HSV-1-tk transgenic mice [4-61 in which elimination of cycling cells is independent of the metabolic pathways of DNA synthesis.…”

Section: Efficiency Of Brdurd Labelingmentioning

confidence: 99%

Accumulation of bromodeoxyuridine‐labeled cells in central and peripheral lymphoid organs: minimal estimates of prodution and turnover rates of mature lymphocytes

et al. 1990

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Daily lymphocyte production in both central and peripheral lymphoid organs was evaluated by associating in vivo incorporation of bromodeoxyuridine (BrdUrd) with cell surface labeling and multi-parameter flow analysis. At least 10% of mature T and B lymphocytes are generated every 24 h. The kinetic behavior of these cell populations differs, however, in that mature B cells are generated predominantly in the precursor compartments of the bone marrow, while most mature T cell generation occurs at the periphery. Therefore, peripheral expansion is the major mechanism of mature T cell production in the adult mouse. By following the accumulation of BrdUrd-labeled cells in peripheral lymphoid organs we found that the progeny of the daily lymphocyte production was sufficient to renew 30%-40% of all peripheral T and B cells every 48 h, demonstrating a high turnover rate of mature lymphocytes. We also examined the conditions of BrdUrd labeling of cycling cells in vivo. We found that while greater than 90% of bone marrow and thymus cells in S phase were labeled with a single injection of BrdUrd, in peripheral lymphoid compartments 70% of T and B cells in S failed to incorporate BrdUrd. Particular schedules of BrdUrd administration were required to overcome the low labeling efficiency of mature cells in vivo. Prolonged BrdUrd administration, however, had toxic effects on resident cells. The low labeling efficiency of BrdUrd incorporation by mature cells, as well as its potential toxicity during prolonged administration, may explain controversial results obtained by the different strategies used to study lymphocyte population dynamics.

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“…This has since been repeatedly confirmed (Sprent & Miller 1972, Ropke & Hougen 1974, Sprent 1974. Continuous infusion of tritiated thymidine into mice has shown that after one day 20% (close to 50% in nude mice), and after 5 days 90% of bone marrow and of thymus lymphocytes are labelled (Ropke & Hougen 1974, Ropke & Everett 1975, Fulop et al 1983.…”

Section: Life Expectancy Of Lymphocytesmentioning

confidence: 99%

Idiotypic Networks and Other Preconceived Ideas

Jerne¹,

Cocteau²

1984

Immunological Reviews

507

199

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The preceding section implies that the immune system (like the brain) reflects first ourselves, then produces a reflection of this reflection, and that subsequently it reflects the outside world: a hall of mirrors. The second mirror images (i.e., stable anti-idiotypic elements) may well be more complex than the first images (i.e., anti-self). Both give rise to distortions (e.g., mutations, gene rearrangements) permitting the recognition of nonself. The mirror images of the outside world, however, do not have permanency in the genome. Every individual must start with self. Paraphrasing Nicolas Schöffer (Schöffer 1982): those who always seek exterior pressures (e.g., microbes) to account for the evolution of the sets of V genes, would do well to turn their vision towards the interiors of themselves, and there discover the mystery, perhaps never completely revealable, of the immune system.

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Life span of small lymphocytes in the thymolymphatic tissues of normal and thymus‐deprived BALB/C mice

Cited by 24 publications

References 23 publications

The bulk of the peripheral B-cell pool in mice is stable and not rapidly renewed from the bone marrow.

The bulk of the peripheral B-cell pool in mice is stable and not rapidly renewed from the bone marrow.

Accumulation of bromodeoxyuridine‐labeled cells in central and peripheral lymphoid organs: minimal estimates of prodution and turnover rates of mature lymphocytes

Idiotypic Networks and Other Preconceived Ideas

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