The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index; none of the 2 sources its claims cite is checked for support yet.
BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death.
Open accessAbstract
The BCL2 protooncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death. BCL2 was isolated from the chromosomal breakpoint of follicular B-cell lymphoma. Transgenic mice that overexpress BCL2 display extended survival of resting B cells. In this study we use a monospecific anti-human BCL2 antibody to define the distribution of BCL2 protein within organized tissues. BCL2 is restricted within germinal centers to the follicular mantle and to portions of the light zone implicated in the selection and maintenance of plasma cells and memory B cells. BCL2 is present in the surviving T cells in the thymic medulla. All hematopoietic lineages that derive from a renewing stem cell also display BCL2. A limited number of nonlymphoid tissues demonstrate BCL2 and can be grouped as (i) glandular epithelium in which hormones or growth factors regulate hyperplasia and involution, (ii) complex differentiating epithelium such as skin and intestine characterized by long-lived stem cells, and (iii) long-lived postmitotic cells such as neurons. Within these tissues that demonstrate apoptotic cell turnover, BCL2 is often topographically restricted to long-lived or proliferating cell zones. BCL2's function as an antidote to apoptosis may confer longevity to progenitor and effector cells in these tissues.
Overview
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Written from the paper’s full text.
TL;DR
Using a monospecific anti-human BCL2 antibody, the authors map BCL2 protein across organized tissues and find it topographically restricted to long-lived or proliferating zones in tissues with apoptotic turnover. BCL2 is present in selected lymphoid, hematopoietic, glandular epithelial, complex epithelial, and postmitotic neuronal compartments.
Key findings
- Within germinal centers, BCL2 is restricted to the follicular mantle and portions of the light zone implicated in selection and maintenance of plasma cells and memory B cells.
- BCL2 is present in surviving T cells in the thymic medulla and in all hematopoietic lineages derived from a renewing stem cell.
- A limited set of nonlymphoid tissues shows BCL2: glandular epithelium regulated by hormones/growth factors, complex differentiating epithelium such as skin and intestine with long-lived stem cells, and long-lived postmitotic cells such as neurons.
- In tissues with apoptotic cell turnover, BCL2 is often topographically restricted to long-lived or proliferating cell zones; the authors suggest BCL2 may confer longevity to progenitor and effector cells.
Methods
- The study uses a monospecific anti-human BCL2 antibody to define BCL2 protein distribution within organized tissues.
- The provided text does not report sample sizes, tissue sources, staining protocols, or quantitative analysis details.
Limitations
- The paper’s abstract does not state limitations.
- Evident from the provided text: only the abstract and reference list are available, so sample composition, antibody specificity controls, quantification, and full results cannot be assessed. No quantitative values are reported in the provided text.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
4 Own interpretation · 4 Own result · 2 No full text of the sources · 1 No basis given
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“All hematopoietic lineages that derive from a renewing stem cell also display BCL2.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“BCL2 is present in the surviving T cells in the thymic medulla.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A limited number of nonlymphoid tissues demonstrate BCL2”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“BCL2 is restricted within germinal centers to the follicular mantle and to portions of the light zone implicated in the selection and maintenance of plasma cells and memory B cells.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Within these tissues that demonstrate apoptotic cell turnover, BCL2 is often topographically restricted to long-lived or proliferating cell zones.”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“glandular epithelium in which hormones or growth factors regulate hyperplasia and involution”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“long-lived postmitotic cells such as neurons”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
In the paper
“Transgenic mice that overexpress BCL2 display extended survival of resting B cells.”
What the sources say
- Not checked — no full text of the sourcecites McDonnell et al., 1989 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“complex differentiating epithelium such as skin and intestine characterized by long-lived stem cells”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“BCL2's function as an antidote to apoptosis may confer longevity to progenitor and effector cells in these tissues.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
- It may state two separate claims as one. 1
In the paper
“The BCL2 protooncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death.”
What the sources say
- Not checked — no full text of the sourcecites Hockenbery et al., 1990 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The anti-human BCL2 antibody used in this study is monospecific for BCL2.
“we use a monospecific anti-human BCL2 antibody”
Citations
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“Bcl-2 protein is effective in preventing apoptosis in a number of physiological and pathological conditions [42, 43], and it has been implicated in the development of malignant lymphomas as well as of nonlymphoid malignancies [44].”
BackgroundAsmarinah, A., Paradowska‐Dogan, A., Kodariah, R., TANUHARDJA, B., Waliszewski, P., Mochtar, C. A., Budiningsih, Y., Weidner, W., & Hinsch, E. (2014) · International Journal of Oncology · doi:10.3892/ijo.2014.2576 · Cited by 36
Expression of p53, Ki-67 and Bcl-2 in parathyroid adenoma and residual normal tissue
Hadar, T., Shvero, J., Yaniv, E., et al. (2005) · Pathology & Oncology Research · doi:10.1007/bf03032405 · Cited by 36
Developmental fates of the mouse germ cell line
Matsui, Y. (1998) · The International Journal of Developmental Biology · doi:10.1387/ijdb.9853835 · Cited by 36
Bcl-2 expression correlates with lymphovascular invasion and long-term prognosis in breast cancer
Neri, A., Marrelli, D., Roviello, F., Marco, G. D., Mariani, F., Stefano, A. D., Megha, T., Caruso, S., Corso, G., Cioppa, T., et al. (2006) · Breast Cancer Research and Treatment · doi:10.1007/s10549-006-9183-2 · Cited by 36
“The bcl-2 gene was initially identified in human B-cell lymphomas and its activity as inhibitor of apoptosis, either drug and p53 induced, in cancer cells has been well demonstrated [10,11].”
BackgroundExpression of BCL‐2 in the developing human fetal and infant breast
Nathan, B., Anbazhagan, R., CLARKSON, P., et al. (1994) · Histopathology · doi:10.1111/j.1365-2559.1994.tb01273.x · Cited by 36
Ning, Z., Norton, J. D., Jin, L., et al. (1996) · European Journal of Immunology · doi:10.1002/eji.1830261013 · Cited by 36
Hanke, J. (2000) · Anatomy and Embryology · doi:10.1007/s004290000112 · Cited by 36
Bcl-2 and Fas, Molecules Which Influence Apoptosis. A Possible Role in Systemic Lupus Erythematosus?
Rose, L. M., Latchman, D. S., & Isenberg, D. A. (1994) · Autoimmunity · doi:10.3109/08916939409010667 · Cited by 36
bcl-2 Expression and Apoptosis in Primary and Metastatic Breast Carcinomas
Villar, E., Redondo, M., Rodrigo, I., a, J. G. I., Avila, E., & Matilla, A. (2001) · Tumor Biology · doi:10.1159/000050608 · Cited by 35
Immunoreactivity of p53, Ki-67, and Bcl-2 in oncocytic adenomas and carcinomas of the thyroid gland
Müller‐Höcker, J. (1999) · Human Pathology · doi:10.1016/s0046-8177(99)90246-0 · Cited by 35
Influence of a Highly Purified Senna Extract on Colonic Epithelium
van Gorkom, B. A. P., Karrenbeld, A., van der Sluis, T., et al. (2000) · Digestion · doi:10.1159/000007743 · Cited by 35
“served as a positive internal control (3p). For p53 staining, no negative control was taken, but a breast carcinoma was taken as positive control (3p).Expression of the p53 and bcl-2 gene were determined light microscopically. Intensity of nuclear staining of p53 and cytoplasmic staining of bcl-2 were described as wea…”
MethodVirág, L., & Szabó, C. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00359-2 · Cited by 35
Failure to down‐regulate Bcl‐2 protein in thymic germinal center B cells in myasthenia gravis
Shiono, H., Fujii, Y., Okumura, M., et al. (1997) · European Journal of Immunology · doi:10.1002/eji.1830270402 · Cited by 35
Silins, S. L., & Sculley, T. B. (1995) · International Journal of Cancer · doi:10.1002/ijc.2910600110 · Cited by 35
Pre-apoptotic Alterations in Hepatocytes of TNF α-treated Galactosamine-sensitized Mice
Angermüller, S., Künstle, G., & Tiegs, G. (1998) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215549804601009 · Cited by 36
“Bcl-2 is a proto-oncogene that blocks programmed cell death (Hockenbery et al. 1990,1991).”
BackgroundAntibody for detecting p53 protein by immunohistochemistry in normal tissues.
Pezzella, F., Micklem, K., Turley, H., et al. (1994) · Journal of Clinical Pathology · doi:10.1136/jcp.47.7.592 · Cited by 35
Insights from transgenic mice regarding the role of bcl -2 in normal and neoplastic lymphoid cells
Cory, S., Harris, A. W., & Strasser, A. (1994) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.1994.0108 · Cited by 35
“much more Bcl-2 protein than do immature cortical cells (Pezzella et al. 1990; Hockenbery et al. 1991), suggesting that modulation of bcl-2 expression plays”
BackgroundA concise review of BCL-2 inhibition in acute myeloid leukemia
Yogarajah, M., & Stone, R. M. (2017) · Expert Review of Hematology · doi:10.1080/17474086.2018.1420474 · Cited by 34
Ito, Y., Takeda, T., Sasaki, Y., et al. (2000) · Oncology · doi:10.1159/000012139 · Cited by 34
“Previous in vivo studies have demonstrated that bcl-2 is detectable in the basal cells of the intestinal epithelium and urothelium [”
ResultReduction of human prostate tumor vascularity by the α1‐adrenoceptor antagonist terazosin
Keledjian, K. M., Borkowski, A., Kim, G., et al. (2001) · The Prostate · doi:10.1002/pros.1083 · Cited by 34
Guillot, C., Coathalem, H., Chetritt, J. J., David, A., Lowenstein, P. R., Gilbert, E., Tesson, L., van Rooijen, N., Cuturi, M. C., Soulillou, J., et al. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.8.5225 · Cited by 34
The Human Immunodeficiency Virus Type-1 (HIV-1) Tat Protein and Bcl-2 Gene Expression
Zauli, G., & Gibellini, D. (1996) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428199609054864 · Cited by 34
Nicot, C., Astier‐Gin, T., & Guillemain, B. (1997) · Virology · doi:10.1006/viro.1997.8720 · Cited by 32
Evidence of significant apoptosis in poorly differentiated ductal carcinoma in situ of the breast
Gandhi, A., Holland, P., Knox, W. F., Potten, C. S., & Bundred, N. J. (1998) · British Journal of Cancer · doi:10.1038/bjc.1998.580 · Cited by 34
The origin of anti-nuclear antibodies in bcl-2 transgenic mice
Mandik‐Nayak, L., Nayak, S., Sokol, C. L., et al. (2000) · International Immunology · doi:10.1093/intimm/12.3.353 · Cited by 34
Taresa, E., Kedei, N., Thomázy, V. A., & Fésüs, L. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35653-9 · Cited by 34
Graph Fourier transform for spatial omics representation and analyses of complex organs
Chang, Y., Liu, J., Jiang, Y. F., Ma, A., Yeo, Y. Y., Guo, Q., McNutt, M. E., Krull, J. E., Rodig, S. J., Barouch, D. H., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-51590-5 · Cited by 32
Kuang, W., Huang, R.-Z., Qin, J.-L., Lü, X., Qin, Q., Zou, B., Chen, Z., Liang, H., & Zhang, Y. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.07.066 · Cited by 34
Morales, E., Ferrer, C., Zuasti, A., et al. (2006) · Journal of Andrology · doi:10.2164/jandrol.106.000778 · Cited by 33
“These results are congruent with previous studies obtained in mouse (Hockenbery et al, 1991; Knudson et al, 1995) and humans (Beumer et al, 2000; Sakamaki, 2003), which suggested that Bcl-2 plays no function in the male gonad in normal conditions, unlike in the ovary, where this protein is critical…”
ResultDifferences of bcl‐2 protein expression between Merkel cells and Merkel cell carcinomas
Moll, I., Gillardon, F., Waltering, S., et al. (1996) · Journal of Cutaneous Pathology · doi:10.1111/j.1600-0560.1996.tb01283.x · Cited by 33
Zhang, T., Zheng, J., Jiang, N., et al. (2009) · Cancer Letters · doi:10.1016/j.canlet.2009.03.025 · Cited by 33
“To elucidate the molecular mechanism of associated with the growth arrest induced by DLC-1, the level of Ki67, Bcl-2, Bax and caspase3 were determined (Fig.”
BackgroundInfluentialThe role of PDGF-dependent suppression of apoptosis in differentiating 3T3-L1 preadipocytes
Staiger, H., & Löffler, G. (1998) · European Journal of Cell Biology · doi:10.1016/s0171-9335(98)80110-6 · Cited by 33
Park, S., Kim, H., & Song, B.-J. (2002) · Pathology & Oncology Research · doi:10.1007/bf03033697 · Cited by 33
Selvakumaran, M., Lin, H., Sjin, R. T. T., et al. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.4.2352-2360.1994 · Cited by 33
Developmentally regulated expression of survivin in the human thymus
Kobayashi, Y., Yukiue, H., Sasaki, H., et al. (2002) · Human Immunology · doi:10.1016/s0198-8859(01)00369-x · Cited by 33
Melanocytes in human skin express bcl‐2 protein
Klein-Parker, H., Warshawski, L., & Tron, V. A. (1994) · Journal of Cutaneous Pathology · doi:10.1111/j.1600-0560.1994.tb00703.x · Cited by 33
Bocchia, M., Xu, Q. L., Wesley, U. V., Xu, Y., Korontsvit, T., Loganzo, F., Albino, A. P., & Scheinberg, D. A. (1997) · Leukemia Research · doi:10.1016/s0145-2126(96)00085-9 · Cited by 33
Wang, S. H., Koenig, R. J., Giordano, T. J., et al. (1999) · Endocrinology · doi:10.1210/endo.140.4.6659 · Cited by 33
Metadata
- Authors
- Hockenbery, D. M., Zutter, M., Hickey, W., Nahm, M., & Korsmeyer, S. J.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1991-08-15
- Volume
- 88
- Issue
- 16
- Pages
- 6961-6965
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC52213
- OpenAlex
- W1970629830
- Semantic Scholar
- d825dc162ad208c572711f59c9aa1c7974e89492
- Cited by
- 1,252
- References
- 40
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 9 · 2022: 4 · 2021: 5 · 2020: 10 · 2019: 9 · 2018: 9 · 2017: 9 · 2016: 7 · 2015: 10 · 2014: 15 · 2013: 10 · 2012: 12
- FWCI
- 26.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- Bcl-2, apoptosis, germinal center, light zone, plasma cells, memory B cells, thymic medulla, hematopoietic stem cells, tissue distribution, epithelial stem cells, follicular B-cell lymphoma, transgenic mice
- MeSH terms
- Adult, Bone Marrow, Breast, Cell Survival, Digestive System, Female, Humans, Immunoenzyme Techniques, Male, Neurons, Pancreas, Prostate, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogenes, Skin, Thymus Gland, Palatine Tonsil, Proto-Oncogene Proteins c-bcl-2
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