The role of PD-L2 in memory B cell responses

• Applicant: Dr. Timm Amendt
• Subject Area: Immunology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 522626652

Immunological memory is required to provide long-lasting protection against re-infecting pathogens and is composed of long-lived plasma cells (LLPC) and memory B cells (MBC). In contrast to LLPC, MBCs often express low affinity B cell receptors (BCR) that are cross-reactive with multiple variants of a pathogen thereby enabling rapid responses to infections with pathogen variants. Despite MBCs forming a repository critically required to ensure long-term protection and showing an unique ability for longevity, mechanisms regulating MBC survival and fate control remain poorly understood. Recently, programmed cell death 1 ligand 2 (PD-L2) was identified to be exclusively expressed by MBCs within the B cell lineage and thus the role of PD-L2 in MBC biology is unknown. PD-L2 may have two distinct functions in MBCs. Firstly, a cell-intrinsic role signalling into MBCs, and secondly, a cell-extrinsic role interacting with PD-1 on T cells leading to their inhibition. Here, we hypothesise that PD-L2 expression is fundamental for maintaining proper MBC function by regulating MBC activation and controlling MBC fate. Further, we propose that PD-L2 mediates immune tolerance by rendering self-reactive MBCs ignorant to autoantigens. In order to test the proposed hypotheses a multidisciplinary approach by using mouse immunology, cellular biology and protein biochemistry will be conducted. Understanding the role of PD-L2 in MBC biology might pave the way for novel therapeutic approaches regarding vaccination or autoimmune diseases.

• DFG Programme: WBP Fellowship
• International Connection: United Kingdom
• Host: Professor Victor Tybulewicz