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

Abstract

Eosinophils were reported to serve as an essential component of the plasma cell niche within the bone marrow. As the potential contribution of eosinophils to humoral immunity has remained incompletely understood, we aimed to further characterize their role during antibody responses and to additionally investigate their role in autoimmune disease. Contrary to our expectations and the currently prevailing paradigm, we found that eosinophils are fully dispensable for the survival of murine bone marrow plasma cells and accordingly do not contribute to antibody production and autoantibody-mediated disease. Littermate wild type and eosinophil-deficient ΔdblGATA-1 animals showed similar numbers and frequencies of plasma cells and did not differ in steady state levels of immunoglobulins or their ability to raise antigen-specific antibody responses. Eosinophils were likewise dispensable for autoantibody production or autoantibody-induced disease in a mouse model of systemic lupus erythematosus. Our findings thus argue against a role of eosinophils during the maintenance of the plasma cell pool and challenge the hitherto postulated concept of an eosinophil-sustained bone marrow niche.

No strict requirement for eosinophils for bone marrow plasma cell survival

“…Although it may not be expected that differences in the mucosal microbiota would influence plasma cell frequencies in the BM, it has long been appreciated that a large fraction of BM PCs in people secrete IgA, and in unpublished data we have noted that overall frequencies of total immature and mature BM plasma cells can vary greatly depending on the animal colony in which the mice in question are housed. Therefore, one potential explanation for the observed discrepancies between Chu et al versus the data reported here and by Haberland et al [20], is that the modest impact of eosinophil loss on BM PC pools can be realized only in the context of additional signals generated by unique collections of microbes. In this regard, it will be important to distinguish the impact of the microbiota on immature versus mature PC pools in the BM and elsewhere.…”

“…versus the data reported here and by Haberland et al. , is that the modest impact of eosinophil loss on BM PC pools can be realized only in the context of additional signals generated by unique collections of microbes. In this regard, it will be important to distinguish the impact of the microbiota on immature versus mature PC pools in the BM and elsewhere.…”

“…These considerations, together with an accompanying report by Haberland et al. in this issue , illustrate that eosinophils are not strictly required to establish or maintain lasting humoral immunity.…”

“…(B [19], the same background strain used by Chu et al Interpretation of these results is limited, however, as these authors did not calculate absolute numbers. These considerations, together with an accompanying report by Haberland et al in this issue [20], illustrate that eosinophils are not strictly required to establish or maintain lasting humoral immunity.…”

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.…”