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.
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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.
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0 of 2 cited sources checked · 0 supported · 0 flagged
- Findingnone given§ Abstract
All hematopoietic lineages that derive from a renewing stem cell also display BCL2.
“All hematopoietic lineages that derive from a renewing stem cell also display BCL2.”
Quote in the paperSubstantial claim- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
- Findingown data§ Abstract
BCL2 protein is present in the surviving T cells in the thymic medulla.
“BCL2 is present in the surviving T cells in the thymic medulla.”
Quote in the paperSubstantial claim- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
- Findingown data§ Abstract
A limited number of nonlymphoid tissues demonstrate BCL2.
“A limited number of nonlymphoid tissues demonstrate BCL2”
Quote in the paperSubstantial claim- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
- Findingown data§ Abstract
BCL2 protein 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 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.”
Quote in the paperSubstantial claim- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
- Findingown data§ Abstract
Within tissues that demonstrate apoptotic cell turnover, BCL2 is often topographically restricted to long-lived or proliferating cell zones.
“Within these tissues that demonstrate apoptotic cell turnover, BCL2 is often topographically restricted to long-lived or proliferating cell zones.”
Quote in the paperSubstantial claim- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
- Interpretationown data§ Abstract
Nonlymphoid tissues demonstrating BCL2 include glandular epithelium in which hormones or growth factors regulate hyperplasia and involution.
“glandular epithelium in which hormones or growth factors regulate hyperplasia and involution”
Quote in the paperSubstantial claim- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
- Interpretationown data§ Abstract
Nonlymphoid tissues demonstrating BCL2 include long-lived postmitotic cells such as neurons.
“long-lived postmitotic cells such as neurons”
Quote in the paperSubstantial claim- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
- Premisecitation§ Abstract
Transgenic mice that overexpress BCL2 display extended survival of resting B cells.
“Transgenic mice that overexpress BCL2 display extended survival of resting B cells.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites McDonnell et al., 1989 source
- Interpretationown data§ Abstract
Nonlymphoid tissues demonstrating BCL2 include complex differentiating epithelium such as skin and intestine characterized by long-lived stem cells.
“complex differentiating epithelium such as skin and intestine characterized by long-lived stem cells”
Quote in the paperSubstantial claim- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
- Interpretationreasoning§ Abstract
BCL2's function as an antidote to apoptosis may confer longevity to progenitor and effector cells in these tissues.
“BCL2's function as an antidote to apoptosis may confer longevity to progenitor and effector cells in these tissues.”
Quote in the paperSubstantial claim- Rests on an assumption: The anti-human BCL2 antibody used in this study is monospecific for BCL2.
- May combine two claims. 1
May combine two claims.
Premisecitation§ AbstractThe BCL2 protooncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death.
“The BCL2 protooncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Hockenbery et al., 1990 source
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”
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Apoptosis (the 1992 Frank Rose Memorial Lecture)
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Self-citationAndrogen receptor status of lymph node metastases from prostate cancer
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Disappearance of the Lymphoid System in Bcl-2 Homozygous Mutant Chimeric Mice
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Targeting of Bcl-2 to the mitochondrial outer membrane by a COOH-terminal signal anchor sequence.
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Ultraviolet radiation and skin cancer: molecular mechanisms
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“In histological studies it has already been established that the majority of T cells in the paracortical areas are bcl-2 + (4, 29).”
Apoptosis regulator Bcl-w is essential for spermatogenesis but appears otherwise redundant
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The significance of spontaneous and induced apoptosis in the gastrointestinal tract of mice
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“How does the tadpole know that the deletion of its tail must stop at the base of its tail? One possibility here is that all cells are programmed to die but specific mechanisms exist to prevent expression of this death [25-27].”
BackgroundApoptosis in myocardial ischaemia and infarction
Krijnen, P., Nijmeijer, R., Meijer, C. J., Visser, C., Hack, C., & Niessen, H. (2002) · Journal of Clinical Pathology · doi:10.1136/jcp.55.11.801 · Cited by 348 · see citing works
Molecular mechanism of stomach carcinogenesis
Tahara, E. (1993) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/bf01212724 · Cited by 324 · see citing works
“Except in the lymphoid and hematopoietic tissues, bcl-2 protein expression is observed preferentially in neurons and epithelial cells that reveal apoptotic cell turnover ( Hockenbery et al. 1991 ).”
BackgroundExpression of the antiapoptosis gene, Survivin, predicts death from recurrent colorectal carcinoma
Sarela, A. I. (2000) · Gut · doi:10.1136/gut.46.5.645 · Cited by 323 · see citing works
“Normally, mitotic activity of large intestinal stem cells located in the basal region of colonic crypts produces a continuous supply of new cells. These cells migrate up the colonic crypt where they differentiate before eventually undergoing apoptosis and exfoliation at the luminal surface. Occurrence of apoptotic act…”
BackgroundLeek, R., Kaklamanis, L., Pezzella, F., et al. (1994) · British Journal of Cancer · doi:10.1038/bjc.1994.22 · Cited by 318 · see citing works
Expression of bcl-2 in fetal tissues suggests a role in morphogenesis.
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Glucocorticoids inhibit apoptosis of human neutrophils
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Regulation of apoptosis in the immune system
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Self-citationApoptosis and cancer chemotherapy
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“In the adult, Bcl-2 expression is limited to renewing stem cell populations, such as those found in hematopoietic lineages, complex differentiating epithelia, and glandular epithelia, and to longlived postmitotic cell populations (Hockenbery et al., 1991).”
BackgroundDevelopmental regulation of the Bcl‐2 protein and susceptibility to cell death in B lymphocytes.
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Self-citationSoluble antigen can cause enhanced apoptosis of germinal-centre B cells
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“Expression of BclII was decreased, which is expected because BclII is anti-apoptotic.(57) Therefore, our results reveal evidence that up-regulation of the Fas/FasL system and activation of the apoptotic cascade are mechanisms of acute and persistent lung damage in ALI or ARDS, and may contribute to leakage of fluid an…”
BackgroundCell Death by Apoptosis in Epidermal Biology
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“This is supported by other studies reporting BCL-2 restriction to tissues such as stem cells, which are long-lived and display a high proliferative capacity.(38) Supporting this view, moving from limbus to the central cornea and from the basal to the superficial layer, cytoplasmic BCL-2 expression decreases in a gradi…”
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Control of programmed cell death in normal and leukemic cells: new implications for therapy
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Bcl-2 inhibits chemotherapy-induced apoptosis in neuroblastoma.
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Apoptosis and hepatobiliary disease
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bcl-2 inhibits apoptosis of neutrophils but not their engulfment by macrophages.
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bcl-2 proto-oncogene expression in normal and neoplastic human myeloid cells
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Apoptosis in sepsis: a new target for therapeutic exploration
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bcl-2: Role in epithelial differentiation and oncogenesis
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Neoteny in Lymphocytes: Rag1 and Rag2 Expression in Germinal Center B Cells
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“44 Days 3246 6 255 (n 5 9) 2169 6 51 (n 5 7) 67* teristic punctate appearance throughout the cytoplasm (Hockenbery et al., 1991; Merry et al., 1994) in motoneuParaffin serial sections (7 mm) of the brain stems from age-matched rons of wild-type animals (Figures 3A, 3C, and 3E), but unlesioned bcl-2 and wild-type anima…”
Background
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-18.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-18.
Statistics and arithmetic are recomputed, not judged.
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