No strict requirement for eosinophils for bone marrow plasma cell survival

Abstract

Lasting antibody responses are maintained by long-lived plasma cells, which are thought to lodge in the BM in specialized survival niches. Eosinophils have been reported to function as a critical component of the BM survival niche where they are thought to provide pro-survival signals to nearby plasma cells. Recent study shows that many BM plasma cells are recently generated and chiefly short-lived cells, raising the possibility that rare plasma cell-eosinophil interactions are a rate-limiting step needed to establish lasting humoral immunity. To address these issues, we examined the impact of eosinophil depletion on short- and long-lived BM plasma cells in the context of antibody responses induced by both T-cell dependent and T-cell independent antigens. Surprisingly, our results failed to support a role for eosinophils in either plasma cell generation or survival. These studies included examination of plasma cell frequencies in mice lacking eosinophils either after antibody-mediated depletion, or due to mutation of the GATA1 locus.

Eosinophils are not essential for maintenance of murine plasma cells in the bone marrow

“…Overall, the present study and the current manuscript by Bortnick et al [22], accompanying our report in the same issue, suggest indicate that the long-time survival of PCs, and thus the long term protection of an organism to previously encountered pathogens, does not depend on a single cellular source of survival factors, but is rather characterized by redundancy and flexibility through a variety of cell types that share the capacity to maintain PC-survival in specialized niches.…”

Plasma cells: You are what you eat

“…134,177,178 Genetic knockout studies, however, have provided mixed results, suggesting that plasma cell-intrinsic signaling by these factors might not all be essential in vivo. [185][186][187][188][189] The integration of these signals with primary plasma cell metabolism, however, has been understudied with a notable recent exception. 178,[180][181][182][183][184] The necessity of some of these cell types and secreted cytokines has been disputed, but a common proposed feature of these populations is their ability to secrete pro-survival cytokines and in turn support plasma cell longevity.…”

“…178,[180][181][182][183][184] The necessity of some of these cell types and secreted cytokines has been disputed, but a common proposed feature of these populations is their ability to secrete pro-survival cytokines and in turn support plasma cell longevity. [185][186][187][188][189] The integration of these signals with primary plasma cell metabolism, however, has been understudied with a notable recent exception. Human plasma cells co-cultured with primary mesenchymal stromal cells (MSCs) survived in in vitro cultures for up to 8 weeks, vs those cultured in media alone, that died within one day.…”

Multiplexed fluorescence microscopy reveals heterogeneity among stromal cells in mouse bone marrow sections

“…The essence of humoral immunity is a stable antibody titer over decades provided by memory plasma cells (mPC). However, there seems to be a high degree of redundancy among the producers of these survival factors (11,12), and also other dynamic accessory cells, such as megakaryocytes (13), basophils (14), or dendritic cells (DCs) (15) are able to promote the survival of mPCs. MPCs reside in a specialized microenvironment in the bone marrow (BM)-the so-called survival niche.…”

“…Eosinophils, which are the dynamic component of the niche with a high turnover (9), contribute to the production of APRIL and BAFF (10). However, there seems to be a high degree of redundancy among the producers of these survival factors (11,12), and also other dynamic accessory cells, such as megakaryocytes (13), basophils (14), or dendritic cells (DCs) (15) are able to promote the survival of mPCs. In addition to those hematopoietic cell types, stromal cells play a crucial role as niche organizers for mPCs.…”