The PD-1 Regulatory Axis Inhibits T Cell-Independent B Cell Memory Generation and Reactivation.

Journal Article (Journal Article)

The inability of T cell-independent type 2 (TI-2) Ags to induce recall responses is a poorly understood facet of humoral immunity, yet critically important for improving vaccines. Using normal and VH B1-8 transgenic mice, we demonstrate that B cell-intrinsic PD-1 expression negatively regulates TI-2 memory B cell (Bmem ) generation and reactivation in part through interacting with PDL1 and PDL2 on non-Ag-specific cells. We also identified a significant role for PDL2 expression on Bmems in inhibiting reactivation and Ab production, thereby revealing a novel self-regulatory mechanism exists for TI-2 Bmems This regulation impacts responses to clinically relevant vaccines, because PD-1 deficiency was associated with significantly increased Ab boosting to the pneumococcal vaccine after both vaccination and infection. Notably, we found a B cell-activating adjuvant enabled even greater boosting of protective pneumococcal polysaccharide-specific IgG responses when PD-1 inhibition was relieved. This work highlights unique self-regulation by TI-2 Bmems and reveals new opportunities for significantly improving TI-2 Ag-based vaccine responses.

Full Text

Duke Authors

Cited Authors

  • Spurrier, MA; Jennings-Gee, JE; Daly, CA; Haas, KM

Published Date

  • October 2021

Published In

Volume / Issue

  • 207 / 8

Start / End Page

  • 1978 - 1989

PubMed ID

  • 34535576

Pubmed Central ID

  • PMC8492549

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.2100336

Language

  • eng