Apoptotic Quality Control of Cellular Competence Limits Cryptic Germinal Center B Cell States
- 1Duke University
Abstract
Germinal center (GC) B cells undergo extensive apoptosis, but how this process shapes evolving GC populations remains unclear. Using mice lacking intrinsic apoptotic effectors BAK and BAX in B cells, we found that mitochondrial apoptosis was dispensable for affinity maturation but critical for controlling GC size and cellular composition, showing that GC population dynamics and affinity maturation can be uncoupled. BAK/BAX-deficient mice mounted enlarged and prolonged GC responses, largely due to the accumulation of non-proliferating Ki-67loCD71lo dark zone (DZ) B cells. CD71hi and CD71lo DZ cells exhibited similar B-cell receptor (BCR) avidity, retained potential for proliferation and plasmacytic differentiation, and shared clonal lineages, indicating recurrent emergence of non-proliferating DZ populations. A subset also carried Somatic-hypermutation-derived defects that abolished antibody expression despite apparently productive V(D)J sequences; reversion of a single amino acid substitution often restored expression. Mitochondrial apoptosis thus enforces cellular quality control in the GC by limiting the persistence of non-proliferating and expression-defective states while remaining dispensable for affinity maturation.
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BibTeX
@misc{yeh2026apoptotic,
title = {{Apoptotic Quality Control of Cellular Competence Limits Cryptic Germinal Center B Cell States}},
author = {C.-H. Yeh and N. Shenkerman and S. Song and H. Kirshner and A. Watanabe and D. Liao and X. Liang and W. Zhang and K. Wiehe and G. Kelsoe and M. Kuraoka},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.10.750694},
url = {https://www.biorxiv.org/content/10.64898/2026.09.10.750694v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Apoptotic Quality Control of Cellular Competence Limits Cryptic Germinal Center B Cell States
AU - C.-H. Yeh
AU - N. Shenkerman
AU - S. Song
AU - H. Kirshner
AU - A. Watanabe
AU - D. Liao
AU - X. Liang
AU - W. Zhang
AU - K. Wiehe
AU - G. Kelsoe
AU - M. Kuraoka
PY - 2026
DA - 2026/09/10
PB - bioRxiv
DO - 10.64898/2026.09.10.750694
UR - https://www.biorxiv.org/content/10.64898/2026.09.10.750694v1
AB - Germinal center (GC) B cells undergo extensive apoptosis, but how this process shapes evolving GC populations remains unclear. Using mice lacking intrinsic apoptotic effectors BAK and BAX in B cells, we found that mitochondrial apoptosis was dispensable for affinity maturation but critical for controlling GC size and cellular composition, showing that GC population dynamics and affinity maturation can be uncoupled. BAK/BAX-deficient mice mounted enlarged and prolonged GC responses, largely due to the accumulation of non-proliferating Ki-67loCD71lo dark zone (DZ) B cells. CD71hi and CD71lo DZ cells exhibited similar B-cell receptor (BCR) avidity, retained potential for proliferation and plasmacytic differentiation, and shared clonal lineages, indicating recurrent emergence of non-proliferating DZ populations. A subset also carried Somatic-hypermutation-derived defects that abolished antibody expression despite apparently productive V(D)J sequences; reversion of a single amino acid substitution often restored expression. Mitochondrial apoptosis thus enforces cellular quality control in the GC by limiting the persistence of non-proliferating and expression-defective states while remaining dispensable for affinity maturation.
ER -