IL-15 stimulates NKG2D while promoting IgM expression of B-1a cells

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2017-07, Vol.95, p.43-50
• Main Authors: Ghosh, Amlan Kanti, Sinha, Debolina, Biswas, Ratna, Biswas, Tapas
• Format: Article
• Language: English
• Subjects: B-1a cells; IgM; Innate signaling; Interleukin-15
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2017.02.014

•IL-15 up-regulates NKG2D and its adaptor DAP10 while activating B-1a cells.•STAT5, p38 and NF-κB are involved in IL-15 mediated signaling of the cells.•Stimulation of IgM transcripts shows IL-15 influence natural antibody response. Interleukin (IL)-15, a key manipulator of T-cell function also modulates B-1a cell activity by augmenting activation markers, turning them towards type 1 polarization and immunoglobulin (Ig) expression which is significant in the context of gut immunity. Here we show, for the first time, IL-15 mediated up-regulation of the activation receptor NKG2D and its adaptor DAP10 in B-1a cells indicating their essential coupling with IL-15 receptor signaling pathway. Our results demonstrate IL-15 treatment increases phosphorylation of STAT5 and p38 leading to translocation of NF-κB onto the nucleus, an attribute that delineates activation of B-1a cells and its role in inflammation. In parallel, increase of anti-apoptotic Bcl-xL suggests its role in long term survival of B-1a cells in culture by IL-15. The cytokine induced overexpression of the plasma cell differentiation transcription factor BLIMP-1 while reducing PAX-5a that could be responsible for the spontaneous Ig secretion by B-1a cells. Up-regulation of IgM transcripts in presence of IL-15 validates mucosal response of the cells through natural Abs to counter pathogens.