Biotin-dependent metabolism controls germinal center fate and vaccine-induced antibody diversification
Abstract
Nutrient availability shapes antibody responses, yet its role in metabolic checkpoints governing germinal center (GC) B-cell differentiation remains incompletely defined. Using heterozygous (HZ) Slc5a6 M60K mice modeling human loss-of-function mutations in the multivitamin transporter SLC5A6, we found that deficient biotin imports impaired mitochondrial metabolism and restricted preGC-to-dark zone progression after vaccination. Single-cell transcriptomics and RNA velocity revealed disrupted GC trajectories, while B-cell receptor repertoire analysis showed impaired class-switch recombination, somatic hypermutation, and vaccine-induced clonal diversity. Spatial multiplexed imaging showed reduced GL7-high GC-associated B-cell regions. Flow cytometric analyses revealed reduced frequencies of RBD-specific B cells and RBD-specific GL7⁺CD95⁺ GC B cells in HZ mice, with higher frequencies after biotin supplementation. Pseudovirus assays demonstrated impaired neutralization of Wuhan-Hu-1 and Omicron BA.2. Dietary biotin supplementation restored GC-associated differentiation, antibody diversification, and vaccine-induced humoral responses. These findings identify biotin-dependent mitochondrial metabolism as an important checkpoint linking micronutrient availability to GC B-cell differentiation and vaccine responsiveness.
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BibTeX
@article{hsieh2026biotindependent,
title = {{Biotin-dependent metabolism controls germinal center fate and vaccine-induced antibody diversification}},
author = {Chu-Han Hsieh and Wilson Aala and Ying-Chen Tsai and Ya-Fang Huang and Miao-Shan Lin and Daw-Yang Hwang and Dar-Bin Shieh and Hsiang-Hsuan Sung and Si-Tse Jiang and Ching-Wei Lin and Chih-An Chen and Michael Warren Hughes and Peng-Chieh Chen and Chi-Chang Shieh},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117999},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03382-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Biotin-dependent metabolism controls germinal center fate and vaccine-induced antibody diversification
AU - Chu-Han Hsieh
AU - Wilson Aala
AU - Ying-Chen Tsai
AU - Ya-Fang Huang
AU - Miao-Shan Lin
AU - Daw-Yang Hwang
AU - Dar-Bin Shieh
AU - Hsiang-Hsuan Sung
AU - Si-Tse Jiang
AU - Ching-Wei Lin
AU - Chih-An Chen
AU - Michael Warren Hughes
AU - Peng-Chieh Chen
AU - Chi-Chang Shieh
PY - 2026
DA - 2026/10/21
JO - iScience
DO - 10.1016/j.isci.2026.117999
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03382-1
AB - Nutrient availability shapes antibody responses, yet its role in metabolic checkpoints governing germinal center (GC) B-cell differentiation remains incompletely defined. Using heterozygous (HZ) Slc5a6 M60K mice modeling human loss-of-function mutations in the multivitamin transporter SLC5A6, we found that deficient biotin imports impaired mitochondrial metabolism and restricted preGC-to-dark zone progression after vaccination. Single-cell transcriptomics and RNA velocity revealed disrupted GC trajectories, while B-cell receptor repertoire analysis showed impaired class-switch recombination, somatic hypermutation, and vaccine-induced clonal diversity. Spatial multiplexed imaging showed reduced GL7-high GC-associated B-cell regions. Flow cytometric analyses revealed reduced frequencies of RBD-specific B cells and RBD-specific GL7⁺CD95⁺ GC B cells in HZ mice, with higher frequencies after biotin supplementation. Pseudovirus assays demonstrated impaired neutralization of Wuhan-Hu-1 and Omicron BA.2. Dietary biotin supplementation restored GC-associated differentiation, antibody diversification, and vaccine-induced humoral responses. These findings identify biotin-dependent mitochondrial metabolism as an important checkpoint linking micronutrient availability to GC B-cell differentiation and vaccine responsiveness.
SN - 2589-0042
ER -