2022
Sci Immunol. 2022 Oct 28;7(76):eabm8389. doi: 10.1126/sciimmunol.abm8389. Epub 2022 Oct 28.
Long-lived plasma cells accumulate in the bone marrow at a constant rate from early in an immune response
Department of Immunology and Pathology, Monash University, Level 6, Burnet Tower, 89 Commercial Road, Melbourne, VIC 3004, Australia. Department of Clinical Haematology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, 305 Grattan St., Parkville, VIC 3000, Australia. Immunology Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, VIC 3050, Australia. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia. Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
Service type: Knock-in mice
Abstract
Vaccines work largely by generating long-lived plasma cells (LLPCs), but knowledge of how such cells are recruited is sparse. Although it is clear that LLPCs preferentially originate in germinal centers (GCs) and relocate to survival niches in bone marrow where they can persist for decades, the issues of the timing of LLPC recruitment and the basis of their retention remain uncertain. Here, using a genetic timestamping system in mice, we show that persistent PCs accrue in bone marrow at an approximately constant rate of one cell per hour over a period spanning several weeks after a single immunization with a model antigen. Affinity-based selection was evident in persisting PCs, reflecting a relative and dynamic rather than absolute affinity threshold as evidenced by the changing pattern of VH gene somatic mutations conveying increased affinity for antigen. We conclude that the life span of persistent, antigen-specific PCs is in part intrinsic, preprogrammed, and varied and that their final number is related to the duration of the response in a predictable way. This implies that modulating vaccines to extend the duration of the GC reaction will enhance antibody-mediated protective immunity.
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