Aranda, C. J. | bioRxiv Science

bioRxiv2025

Long-lived IgE plasma cells that reside in the spleen contribute to the persistence of the IgE response

IgE plasma cells (PC) producing high affinity antibodies are critical players in allergic diseases. Allergies may persist or resolve over time, but the factors involved in their evolution are not well known. Sustained production of IgE antibodies, even in the absence of allergen exposure in persistent allergy, suggests the existence of long-lived IgE PC. However, the ability of IgE PC to undergo terminal differentiation and become long-lived has been questioned. Here we demonstrate that IgE PC undergo swift maturation into non-dividing MHCIIlowCD93+CD98high PC in immunized mice. Mature IgE PC have a distinct transcriptional profile for adaptation to high protein synthesis, glycosylation, and survival. Using PC timestamping, long-lived IgE PC could be found several months after immunization in mice. Remarkably, the spleen rather than the bone marrow, was a main tissue of residence of mature long-lived IgE PC. Our findings provide key insights to understand IgE production in persistent allergy. HighlightsO_LIIgE PC form in a narrow window after immunization and undergo swift maturation. C_LIO_LITimestamping reveals the existence of CD93+CD98highMHCIIlow long-lived IgE PC. C_LIO_LIThe spleen and lymph nodes are the main tissues of mature IgE PC residence. C_LIO_LIIgE PC use distinct adaptations to high antibody secretion and survival. C_LI

immunology↗

bioRxiv2024

Ovalbumin-loaded mesoporous silica nanoparticles for allergen specific immunotherapy

Allergic diseases are caused by an unnecessary immune response against harmless external substances (allergens), and they pose an important economic burden for healthcare systems with a large impact on the quality of life of patients. Allergen-specific immunotherapy (AIT) is the only treatment option capable of modifying the natural history of the disease, but current AIT schemes present safety and efficacy limitations. One possible strategy to address these limitations is to encapsulate the allergen in nanoparticle carriers that can deliver it to antigen presenting cells while hiding it from effector cells responsible for the allergic reaction. In this work, we evaluate the use of allergen-loaded mesoporous silica nanoparticles (MSNs) as AIT agents. MSNs of different pore sizes were prepared and characterized, evaluating their capacity to load and release ovalbumin (OVA) as a model allergen. Extra-large pore MSNs (XL-MSNs) showed the optimal loading and release behavior, presenting also enhanced activation of the dendritic cell line DC2.4 and reduced allergenic capacity in pre-sensitized RBL-2H3 cells, both compared to free OVA. After evaluating their biodistribution following subcutaneous, sublingual or intravenous administration, their therapeutic potential in AIT was further assessed in an in vivo murine model of OVA systemic anaphylaxis. The results showed that intravenous administration of OVA-loaded XL-MSNs significantly protected the mice from anaphylaxis and induced a Th1/Treg-immune profile, while administration through other routes failed to prevent the development of an anaphylactic reaction upon provocation with OVA. These findings establish MSNs, particularly via intravenous administration, as a promising platform to develop safer and more effective AIT.

immunology↗