Organization of immunological memory by bone marrow stroma

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. How are memory cells maintained? In this Review, the authors discuss the emerging role of mesenchymal stromal cells — which organize defined numbers of dedicated survival niches for different types of memory lymphocytes — in the maintenance of immunological memory. 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 syste