CHK1 dosage in germinal center B cells controls humoral immunity.

ABSTRACT: Germinal center (GC) B cells are among the fastest replicating cells in our body, dividing every 4-8 h. DNA replication errors are intrinsically toxic to cells. How GC B cells exert control over the DNA damage response while introducing mutations in their antibody genes is poorly understood. Here, we show that the DNA damage response regulator Checkpoint kinase 1 (CHK1) is essential for GC B cell survival. Remarkably, effective antibody-mediated immunity relies on optimal CHK1 dosage. Chemical CHK1 inhibition or loss of one Chk1 allele impairs the survival of class-switched cells and curbs the amplitude of antibody production. Mechanistically, active B cell receptor signaling wires the outcome of CHK1-inhibition towards BIM-dependent apoptosis, whereas T cell help favors temporary cell cyc

SUBMITTER: Schoeler K 

PROVIDER: S-EPMC7224292 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature