Abstract
The bone marrow (BM) is key to protective immunological memory because it harbors a major fraction of the body’s plasma cells, memory CD4+ and memory CD8+ T-cells. Despite its paramount significance for the human immune system, many aspects of how the BM enables decade-long immunity against pathogens are still poorly understood. In this review, we discuss the relationship between BM survival niches and long-lasting humoral immunity, how intrinsic and extrinsic factors define memory cell longevity and show that the BM is also capable of adopting many responsibilities of a secondary lymphoid organ. Additionally, with more and more data on the differentiation and maintenance of memory T-cells and plasma cells upon vaccination in humans being reported, we discuss what factors determine the establishment of long-lasting immunological memory in the BM and what we can learn for vaccination technologies and antigen design. Finally, using these insights, we touch on how this holistic understanding of the BM is necessary for the development of modern and efficient vaccines against the pandemic SARS-CoV-2.
Highlights
These results suggest that the majority of stromal cells cannot host more than one memory cell
With the bone marrow (BM) being such a central organ accommodating a multitude of different kinds of cells, the presentation of antigens and initiation of primary responses—functions typically restricted to SLO—seems to be a possible scenario
The BM’s contributions toward a protective immune system only start there, as memory maintenance occurs in the BM [2,9]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The physiological challenges for each individual memory cell are enormous: They need to be able to self-renew, persist long-term and give rise to highly proliferative progeny while staying capable of quickly mounting a recall response upon reinfection [1,2]. The kinetics of cell migration are an important factor that needs precise adjustment [5,6]. We take a look at how the BM plays a pivotal role in establishing long-lasting immune memory and sustaining protection despite the aforementioned obstacles. (See Table 1 for a list of all of the important molecular factors described in this review.) we hypothesize that the BM is the central site where the threads of maintaining memory cells, inducing primary immune responses to systemic infections as well as secondary immune responses converge
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