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Publication : Impaired development of memory B cells and antibody responses in humans and mice deficient in PD-1 signaling.

First Author  Ogishi M Year  2024
Journal  Immunity Volume  57
Issue  12 Pages  2790-2807.e15
PubMed ID  39603236 Mgi Jnum  J:360155
Mgi Id  MGI:7790378 Doi  10.1016/j.immuni.2024.10.014
Citation  Ogishi M, et al. (2024) Impaired development of memory B cells and antibody responses in humans and mice deficient in PD-1 signaling. Immunity 57(12):2790-2807.e15
abstractText  T follicular helper (Tfh) cells abundantly express the immunoreceptor programmed cell death protein 1 (PD-1), and the impact of PD-1 deficiency on antibody (Ab)-mediated immunity in mice is associated with compromised Tfh cell functions. Here, we revisited the role of the PD-1-PD-L1 axis on Ab-mediated immunity. Individuals with inherited PD-1 or PD-L1 deficiency had fewer memory B cells and impaired Ab responses, similar to Pdcd1(-/-) and Cd274(-/-)Pdcd1lg2(-/-) mice. PD-1, PD-L1, or both could be detected on the surface of human naive B cells following in vitro activation. PD-1- or PD-L1-deficient B cells had reduced expression of the transcriptional regulator c-Myc and c-Myc-target genes in vivo, and PD-1 deficiency or neutralization of PD-1 or PD-L1 impeded c-Myc expression and Ab production in human B cells isolated in vitro. Furthermore, B cell-specific deletion of Pdcd1 prevented the physiological accumulation of memory B cells in mice. Thus, PD-1 shapes optimal B cell memory and Ab-mediated immunity through B cell-intrinsic and B cell-extrinsic mechanisms, suggesting that B cell dysregulation contributes to infectious and autoimmune complications following anti-PD-1-PD-L1 immunotherapy.
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