The establishment of the plasma cell survival niche in the bone marrow.

Antibodies continuously secreted by plasma cells play a central role in humoral immune protection of the organism. These plasma cells are generated during the germinal center reaction, and it is likely that they here acquire the potential to develop into long-lived cells. To achieve longevity, these cells require factors provided by the microenvironment. Indeed, only a few of the plasmablasts arising during an immune response will differentiate into mature plasma cells, which may survive for decades in specialized survival niches in the bone marrow. Here, we discuss how the survival niche in the bone marrow is established and what is known about the cell-cell interactions needed to support the long-term survival of plasma cells. A particular emphasis is put on the role of eosinophils, which have been shown to be key providers of plasma cell survival factors. The data suggest that the reticulum of bone marrow stromal cells supports a dynamic survival niche, in which long-lived plasma cells are provided with essential factors by a continuously turning over population of eosinophils and other cells.

Immunization induces activation of bone marrow eosinophils required for plasma cell survival.

Eosinophils not only have multiple functions as effector cells of the innate immune system but also as modulators of immune responses. As producers of cytokines required for plasma cell survival, they are essential for the long-term maintenance of plasma cells in the BM. Here we show that the activation of eosinophils both in vitro and in vivo enhances the expression of the plasma cell survival factors APRIL, IL-6, IL-4, IL-10 and TNF-α. The in vivo activation of eosinophils was independent of the type of adjuvant used for primary immunization. Although eosinophils were activated by adjuvant itself, a stable activation and a constant increase in BM eosinophils were observed only in the presence of antigen. Thus, the numbers and the quality of eosinophils were dependent on priming the adaptive immune system. With secondary immunization and re-activation of antigen-dependent memory cells, the ability of eosinophils to promote plasma cell survival was further increased. These findings suggest that in T-cell-dependent immune responses eosinophils are conditioned to support the long-term survival of plasma cells in the BM, and furthermore imply that through accelerated numbers of eosinophils, stable plasma cell survival niches are established and the long-term survival of plasma cells is ensured.