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Organization of immunological memory by bone marrow stroma

Nature Reviews Immunology volume 10, pages 193–200 (2010)Cite this article

Subjects

Key Points

  • The important role of stromal cells in the regulation of immune responses is becoming increasingly appreciated. In addition to providing a supportive lattice for lymphocytes by expressing adhesion molecules, the stroma directs lymphocyte migration by secreting chemokines and can interact with lymphocytes through cytokine secretion.

  • In addition to the relevance of stromal cells in the initiation of immune responses, there is evidence that these cells regulate the generation and maintenance of immunological memory. Follicular dendritic cells are involved in the generation of memory B cells and plasma cells during germinal centre reactions.

  • Bone marrow stroma is thought to have a role in the maintenance of several types of memory lymphocytes. It is composed of mesenchymal stromal cells, endothelial cells, osteoblasts and adipocytes.

  • Long-lived plasma cells have been shown to dock on a subpopulation of CXCL12+VCAM1+ mesenchymal stromal cells that is thought to form specific survival niches for those cells, thus regulating the size of the memory plasma cell compartment. Resting memory CD4+ T cells also reside in the bone marrow but, in contrast to plasma cells, they are found in close association with IL-7+VCAM1+ stromal cells.

  • Memory B cells are thought to be localized in the spleen, but their microanatomical niche has not been defined in detail. The localization of resting memory CD8+ T cells is currently unclear.

  • A deeper understanding of stromal cell populations and subpopulations in different anatomical locations is necessary to identify the molecular mechanisms involved in the maintenance of immunological memory.

Abstract

Immunological memory is a hallmark of the adaptive immune system. Plasma cells and memory B and T cells collectively provide protective immunity and effective secondary immune responses to invading pathogens. Here, we discuss how mesenchymal stromal cells regulate immunological memory by organizing defined numbers of dedicated survival niches for plasma cells and memory T cells in the bone marrow and also, to a lesser extent, in secondary lymphoid organs. An understanding of the biology of mesenchymal stromal cells and their interaction with cells of the immune system is key to fully understanding immunological memory.

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Figure 1: Overall organization of bone marrow stroma.
Figure 2: Development of bone marrow stromal cells and their role in B cell ontogeny and memory maintenance.

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Acknowledgements

We thank S. Zehentmeier, A. Hanazawa, H.-D. Chang, T. Doerner, A. Hegazy, F. Hiepe and M. Löhning for valuable discussions. This work was supported by grants: SFB 421, SFB 633 and SFB 650 of the German Research Foundation (DFG). K.T. was a research fellow of the Alexander von Humboldt foundation.

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Authors and Affiliations

  1. German Rheumatism Research Center (DRFZ), A Leibniz Institute, Berlin, 10117, Germany

    Koji Tokoyoda, Anja E. Hauser & Andreas Radbruch

  2. Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, 2608670, Chiba, Japan

    Koji Tokoyoda & Toshinori Nakayama

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  1. Koji Tokoyoda
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  2. Anja E. Hauser
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  3. Toshinori Nakayama
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  4. Andreas Radbruch
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Correspondence to Andreas Radbruch.

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Deutsches Rheuma-Forschungzentrum (DRFZ), A Leibniz Institute homepage

Glossary

Stromal cells

Cells of non-lymphoid origin that form the framework of each organ. These cells can support adhesion, proliferation and survival of distinct cell subsets.

Central tolerance

Tolerance to self that is created at the level of the central lymphoid organs. Developing T cells (in the thymus), and B cells (in the bone marrow) that strongly recognize self antigen face deletion or marked suppression.

Follicular dendritic cell

A cell type that is normally found only in the germinal centres of lymphoid tissue. It presents antigen to selected B cells and provides survival signals required for affinity maturation.

Memory B cell

An antigen-experienced B cell that expresses high-affinity antibodies and quickly differentiates into a plasma cell in antigen recall responses.

Plasma cell

A terminally differentiated quiescent B cell that develops from a plasmablast and is characterized by an ability to secrete large amounts of antibody.

Sinusoid

A specialized blood vessel in haematopoietic tissues through which venous circulation occurs. It has thin walls formed by a discontinuous, irregularly shaped endothelium that allows cells to pass in and out of circulation.

Germinal centre

A lymphoid structure that arises within follicles after immunization with, or exposure to, a T cell-dependent antigen. It is specialized for facilitating the development of high-affinity, long-lived plasma cells and memory B cells.

High endothelial venule

A specialized venule that occurs in secondary lymphoid organs, except the spleen. High endothelial venules allow continuous transmigration of lymphocytes as a consequence of the constitutive expression of adhesion molecules and chemokines their luminal surface.

Plasmablast

A dividing antibody-secreting cell of the B cell lineage that has migratory potential. These cells can further mature into plasma cells, which do not divide.

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Tokoyoda, K., Hauser, A., Nakayama, T. et al. Organization of immunological memory by bone marrow stroma. Nat Rev Immunol 10, 193–200 (2010). https://doi.org/10.1038/nri2727

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