Single-cell NAD(H) levels predict clonal lymphocyte expansion dynamics.
Sci Immunol
; 9(93): eadj7238, 2024 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-38489349
ABSTRACT
Adaptive immunity requires the expansion of high-affinity lymphocytes from a heterogeneous pool. Whereas current models explain this through signal transduction, we hypothesized that antigen affinity tunes discrete metabolic pathways to license clonal lymphocyte dynamics. Here, we identify nicotinamide adenine dinucleotide (NAD) biosynthesis as a biochemical hub for the T cell receptor affinity-dependent metabolome. Through this central anabolic role, we found that NAD biosynthesis governs a quiescence exit checkpoint, thereby pacing proliferation. Normalizing cellular NAD(H) likewise normalizes proliferation across affinities, and enhancing NAD biosynthesis permits the expansion of lower affinity clones. Furthermore, single-cell differences in NAD(H) could predict division potential for both T and B cells, before the first division, unmixing proliferative heterogeneity. We believe that this supports a broader paradigm in which complex signaling networks converge on metabolic pathways to control single-cell behavior.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos
/
NAD
Idioma:
En
Revista:
Sci Immunol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos