Inhibitors of elastase stimulate murine B lymphocyte differentiation into IgG‐ and IgA‐producing cells

Abstract

It is well established that dendritic cells and macrophages play a role in antigen presentation to B and T cells and in shaping B and T cell responses via cytokines they produce. We have previously reported that depletion of neutrophils improves the production of mucosal IgA after sublingual immunization with Bacillus anthracis edema toxin as adjuvant. These past studies also demonstrated that an inverse correlation exists between the number of neutrophils and production of IgA by B cells. Using specific inhibitors of elastase, we addressed whether the elastase activity of neutrophil could be the factor that interferes with production of IgA and possibly other immunoglobulin isotypes. We found that murine splenocytes and mesenteric lymph node cells cultured for 5 days in the presence of neutrophil elastase inhibitors secreted higher levels of IgG and IgA than cells cultured in the absence of inhibitors. The effect of the inhibitors was dose-dependent and was consistent with increased frequency of CD138 cells expressing IgG or IgA. Finally, neutrophil elastase inhibitors increased transcription of mRNA for AID, IL-10, BAFF and APRIL, factors involved in B cell differentiation. These findings identify inhibitors of elastase as potential adjuvants for increasing production of antibodies.

Inhibition of elastase enhances the adjuvanticity of alum and promotes anti–SARS-CoV-2 systemic and mucosal immunity

“…We also tested whether NEI could regulate immune factors in other animal species. We previously showed that NEI stimulates the expression of BAFF and IL-10 and secretion of IgG and IgA by murine spleen cells, in vitro ( 25 ). Addition of NEI to cultures of pig spleen cells stimulated IgG and IgA secretion ( SI Appendix , Fig.…”

“…NEI induction of antibody-stimulating cytokines BAFF and IL-10 ( SI Appendix , Fig. S3 ) ( 25 ) could be the accelerating factor. NEI supplementation or lack of elastase could facilitate the migration of vaccine-primed cells, as suggested by others who showed that depletion of neutrophils favors the development of T responses at distant lymph nodes ( 33 ).…”

“…To our knowledge, this is evidence that the adjuvanticity of alum can be modulated to allow the development of mucosal immunity and more specifically antigen-specific SIgA in mucosal tissues and secretions. We have previously shown that NEI stimulates expression of IgA-promoting cytokines IL-10 and TGFβ by murine spleen cells ( 25 ). The fact that NEI stimulates expression of these cytokines by human PBMCs ( SI Appendix , Fig.…”

Citric Acid Promoting B Lymphocyte Differentiation and Anti-epithelial Cells Apoptosis Mediate the Protective Effects of Hermetia illucens Feed in ETEC Induced Piglets Diarrhea

“…When the inactivated B cells are stimulated by an antigen via IgM, these cells undergo Ig class switching recombination (CSR) to produce antibodies of different isotypes but having the same antigen specificity as IgM, such as IgA and IgG ( 29 ). Many cells provide the costimulation and cytokine signals required by IgCSR and B cells to produce antibodies ( 29 ).…”

Targeting peptide‐enhanced antibody and CD11c+dendritic cells to inclusion bodies expressing protective antigen against ETEC in mice

“…Then, the targeting peptide of M cells and the DCs favored the T h 1-cell response (54), which stimulates the expansion of germinal center B cells for anti-ETEC-specific antibody production (55). It is well established that DCs and macrophages play a role in antigen presentation to Band T-cells and in shaping B and T cell responses to produce mucosal IgA after sublingual immunization with Bacillus anthracis edema toxin as an adjuvant (56). Various studies have shown that antigens target different molecules, which results in different immune responses.…”