PD-L1 expression in germinal centers promotes humoral immunity by restricting T follicular regulatory cell differentiation.

PD-L1 expressed by B cell zone reticular cells in germinal centers promotes humoral immunity by restricting T follicular regulatory cell differentiation, enabling stronger GC formation.

• Why it matters: The ligand PD-L1’s role in germinal centers is unclear despite PD-1 being highly expressed on TFH and TFR cells, limiting understanding of how T–B collaboration shapes immunity.
• What they did: Integrated analyses of secondary lymphoid organs identified PD-L1 on BRCs, and BRC-specific PD-L1 deletion increased TFH Sostdc1 production and TFR differentiation while destabilizing T–B contacts.
• The result: PD-L1 loss enhanced GC-linked autoantibody tolerance breakdown and, in tumor biopsies, a tumor-infiltrating TFH SOSTDC1 signature inversely correlated with immunotherapy responsiveness, suggesting PD-L1 blockade may be improved by augmenting B cell responses.

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