Abstract
The generation of long-lived antibody-secreting cells (ASC) and memory B cells are critical events for an effective vaccine and the choice of adjuvant can influence these processes. Various cellular and molecular mechanism involved in the protease action that determine Th2 responses have been identified. However, direct or indirect actions in the regulation of the induction, survival and longevity of ASC in differential compartments remain largely unknown. We investigated whether the proteolytic activity of proteins are determinant for the modulation of the memory immune response in mice, promoting the differentiation of memory B cells to terminally differentiated end stage cells. Here, we show that the proteolytic activity of Natterins, from the venom of Thalassophryne nattereri Brazilian fish, besides inducing a Th2 response with plasmatic titers of high-affinity antigen-specific IgE over extended periods is sufficient for the generation of signals that contribute to the formation of a survival niche in the spleen, essential for the longevity of the main subtype of ASC with B220neg phenotype.
Highlights
Type I IgE-mediated hypersensitivity reactions, a classical prototype Th2 polarized response, are initiated by the recognition of allergens by dendritic cells (DC), and culminate in Th2 cell differentiation, IgE antibodies (Abs) production, and mast cell sensitization and triggering
Because Natterins activates B2 cells, and this cell type can contribute to GC reactions or become antibody-secreting cells (ASC) in the presence of TLR agonists or infections [31,6], we examined whether Natterins induces GC memory B cell and plasma cell (ASC with positive or negative expression of B220) development
Much is known about the cellular and molecular mechanism involved in the protease action that determine Th2 polarized responses [14], their direct or indirect actions in the regulation of the induction and survival of Ab-producing memory B cells or ASC in differential compartments remain largely unknown
Summary
Type I IgE-mediated hypersensitivity reactions, a classical prototype Th2 polarized response, are initiated by the recognition of allergens by dendritic cells (DC), and culminate in Th2 cell differentiation, IgE antibodies (Abs) production, and mast cell sensitization and triggering. Part of the peripheral B cell compartment has undergone class switching to IgE. Because long-lived antibody-secreting cells (ASC) are the source of IgE, recruitment and selection of memory B cells (Bmem) into the ASC compartment is a critical step in immune deregulation that leads to the production of IgE. ASC (positive for syndecan-1– CD138) are terminally differentiated and continue secreting high affinity antigen-specific Abs for protracted periods of time without antigenic stimulation in the bone marrow (BM) that provides a special microenvironment for their longevity [5]
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