Evidence map›Paper›PMID 42501330›Full record

ArticleCell reports2026

Distributed clonal deletion prevents autoimmune disease progression.

Anna M Newen, Uzair A Ansari, Mikala J Simpson, Fiona Flynn, Sukriti Sharma, Michael Ivanov, Ishaan Antani, Dylan Pfannenstiel, Baktiar Karim, Laura Bassel and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Anna M NewenExperimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health; Bethesda, MD 20892, USA.
Uzair A AnsariExperimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health; Bethesda, MD 20892, USA.
Mikala J SimpsonExperimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health; Bethesda, MD 20892, USA.
Fiona FlynnExperimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health; Bethesda, MD 20892, USA.
Sukriti SharmaExperimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health; Bethesda, MD 20892, USA.
Michael IvanovExperimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health; Bethesda, MD 20892, USA.
Ishaan AntaniExperimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health; Bethesda, MD 20892, USA.
Dylan PfannenstielExperimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health; Bethesda, MD 20892, USA.
Baktiar KarimMolecular Histopathology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
Laura BasselMolecular Histopathology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
Brian CapaldoComputational Genomics and Bioinformatics Branch, National Cancer Institute, National Institutes of Health, Frederick, MD 20850, USA.
Qingrong ChenComputational Genomics and Bioinformatics Branch, National Cancer Institute, National Institutes of Health, Frederick, MD 20850, USA.
Daoud MeerzamanComputational Genomics and Bioinformatics Branch, National Cancer Institute, National Institutes of Health, Frederick, MD 20850, USA.
Indu RamanMicroarray and Immune Phenotyping Core Facility, University of Texas, Southwestern Medical Center, Dallas, TX 75235, USA.
Chengsong ZhuMicroarray and Immune Phenotyping Core Facility, University of Texas, Southwestern Medical Center, Dallas, TX 75235, USA.
Cornelius Y TaabazuingDepartment of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Hamid KashkarInstitute for Molecular Immunology, Center for Molecular Medicine Cologne, CECAD Research Center, Medical Faculty, University of Cologne, 50935 Cologne, Germany.
Christian T MayerExperimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health; Bethesda, MD 20892, USA. Electronic address: christian.mayer@nih.gov.

Funding

The role of apoptosis in B lymphocyte biologyZIABC011975 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MAYER, CHRISTIAN · 2020 to 2025
$5.2M
Intramural NIH HHS Z99 CA999999Intramural NIH HHS ZIA BC011975
6 · The paper itself

Abstract

Self-reactive B cells arise during development and can increase pathogenicity through activation-induced cytidine deaminase (AID)-mediated diversification. Clonal deletion is thought to eliminate these cells, yet how deletion is distributed across developmental and activation stages to prevent autoimmune disease remains unclear. Here, we show that self-tolerance is enforced through temporally distinct mitochondrial outer membrane permeabilization (MOMP) checkpoints. Using conditional Bcl-2 expression to inhibit MOMP either from B cell development or activation, we find that early inhibition permits survival of autoreactive B cells after peripheral egress, expanding the pool available for activation and AID-dependent diversification. This results in broadened class-switched IgG autoreactivity, complement activation, kidney pathology, and drives lethal autoimmune disease. In contrast, post-activation MOMP inhibition promotes autoreactive cell accumulation and autoantibody production but causes limited tissue damage and normal survival. Together, these findings support a Distributed Clonal Deletion Model in which temporally distinct checkpoints cooperate to constrain autoimmune disease progression.

Indexed as

activation-induced cytidine deaminaseAIDautoimmunityB cell toleranceclonal deletionCP: immunologygerminal centermitochondrial outer membrane permeabilizationMOMPSLEsystemic lupus erythematosus

Identifiers

PMID42501330
PMCPMC13575929

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.