Adaptive B cell immunity to environmental antigens must be regulated by multiple CD4 T cell dependent tolerance mechanisms. Using integrated single cell strategies, we demonstrate that acute PD-1 blockade induces extensive and selective local anti-inflammatory IgG1 plasma cell (PC) differentiation. Expansion of pre-existing IgG1 germinal center (GC) B cell and enhanced GC programming without memory B cell involvement reveals an isotype-specific GC checkpoint that blocks steady-state IgG1 antibody maturation. While there was no adjuvant impact on immunization, acute PD-1 checkpoint blockade exaggerates anti-commensal IgG1 antibody production, alters microbiome composition and exerts its action in a CD4 T cell dependent manner. These findings reveal a PD-1 controlled adaptive B cell tolerance checkpoint that selectively constrains maturation of pre-existing anti-inflammatory antibodies to prevent over-reaction to steady-state foreign antigens.
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