Rethinking ‘immunological memory’: Local and systemic immunity provided by bone marrow‐resident memory cells

Abstract

AbstractIt has been 25 years since we first described long‐lived memory plasma cells of the bone marrow, 13 years since we identified bone marrow resident memory T cells and 2 years since we showed that the bone marrow is also a preferred location of resident memory B cells. The bone marrow is increasingly recognized as a fundamental component of long‐lasting immunological memory, not only providing protective immunity but also fuelling chronic inflammation. We now understand that the bone marrow functions as the ‘backbone’ of immunological memory, hosting the memory plasma cells which provide not only humoral immunity but also memory B and T cells, which constitute ‘reactive memory’. This knowledge now allows us to define true cellular ‘correlates of protection’ for systemic immunity, its quality and duration, as induced by infection and vaccination, something that has never been more important given the recent SARS‐CoV‐2 pandemic. While memory plasma cells of the bone marrow indicate long‐lasting humoral protection, memory T (and B) cells mobilized into the blood in secondary immune reactions indicate the strength of reactive memory. In this review, we have contextualized many of our own findings from the last two decades that have contributed to our understanding of how bone marrow‐resident memory cells provide local and systemic immunity.