The Influence of B-Cell Intrinsic IL-1β on the Long-Term Maintenance of Antibody Secreting Cells 2257827

Abstract

Abstract Introduction Antibody secreting cells (ASCs) are an integral component of immunological memory and can play a pathogenic or protective role in the setting of autoimmunity or infection, respectively. Long-term survival of ASCs, and thus durability of the antibody response, is dependent on the microenvironment in the bone marrow (BM). In vitro studies have shown that mesenchymal stem cells (MSCs) express interleukin 1 receptor (IL1R1) and produce ASC survival factor interleukin 6 (IL-6) upon stimulation with interleukin 1β (IL-1β). IL-1β is a key pro-inflammatory cytokine that has typically been associated with innate immune cells, though our group has demonstrated B cells as a source of IL-1β in the germinal center. Thus, its presence on B cells raises questions about the role of IL-1β in modulating adaptive immune responses. As cytokines have been shown to function locally, we hypothesize ASCs as a source of IL-1β in the BM, enhancing their survival and homeostasis. Methods To explore the role of B cell derived IL-1β on ASC maintenance in the BM we utilized a murine B cell specific depletion of IL-1 β in the setting of influenza infection to assess ASC response. Results In wild type mice we observe that >90% of BM ASCs express IL-1β and that BM ASCs express IL-1β at higher levels than peripheral ASCs. In the setting of B cell intrinsic IL-1β deficiency we observe a significant decrease in all ASCs and antigen specific ASCs in the BM at 40 days post influenza infection. This decrease was specific to the BM and was not noted in the lymph node. Conclusion Hence, B cell derived IL-1β is vital for optimal long-term maintenance of ASCs in the BM post influenza infection and thus implicates the role of this cytokine in durable antibody-mediated memory. Subsequent studies will further probe the dependence of ASC homeostasis in the BM on B cell derived IL-1β as well as the potential role of agonistic effects on its cognate receptor IL1R1 on MSCs to produce IL-6 on ASC survival and maintenance in the BM. Funding Source n/a Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)