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

• Published in: European journal of immunology 2018-08, Vol.48 (8), p.1295-1301
• Main Authors: Attia, Zayed, Rowe, John C., Kim, Eunsoo, Varikuti, Sanjay, Steiner, Haley E., Zaghawa, Ahmad, Hassan, Hany, Cormet‐Boyaka, Estelle, Satoskar, Abhay R., Boyaka, Prosper N.
• Format: Article
• Language: English
• Subjects: Adjuvants; Animals; Antigen presentation; APRIL protein; B cells; B-Cell Activating Factor - genetics; B-Lymphocytes - immunology; BLyS protein; Cell differentiation; Cell Differentiation - immunology; Cells, Cultured; Dendritic cells; Edema; Elastase; Glycine - analogs & derivatives; Glycine - pharmacology; Immunization; Immunoglobulin A; Immunoglobulin A - biosynthesis; Immunoglobulin class switching; Immunoglobulin G; Immunoglobulin G - biosynthesis; Inhibitors; Interleukin-10 - genetics; Isotypes; Leukocytes (neutrophilic); Lymph nodes; Lymph Nodes - cytology; Lymph Nodes - metabolism; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes B; Lymphocytes T; Macrophages; Mice; Mice, Inbred C57BL; Mucosa; Neutrophil elastase inhibitor; Neutrophils; Neutrophils - immunology; Pancreatic Elastase - antagonists & inhibitors; RNA, Messenger - biosynthesis; Serine Proteinase Inhibitors - pharmacology; Spleen - cytology; Spleen - metabolism; Splenocytes; Sulfonamides - pharmacology; Syndecan-1 - metabolism; Transcription; Tumor Necrosis Factor Ligand Superfamily Member 13 - genetics
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201747264

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. Addition of neutrophil elastase inhibitors (NEI) to cultures of murine splenocytes and mesenteric lymph node cells increases the transcription of mRNA for AID, IL‐10, BAFF and APRIL, and secretion of IgG and IgA. These results suggest that NEI could represent a new class of adjuvant for enhancing responses to vaccines.