CD209 activation promotes survival of lymphoblastic human B cells

Abstract

Abstract The role of B cells in host protection and antibody production depends in part on their ability to recognize antigens and pathogen associated molecular patterns (e.g. carbohydrates and nucleic acids) mostly through membrane bound receptors. CD209 (i.e. DC-SIGN) is a C-type lectin receptor expressed on dendritic cells, macrophages and B cells which binds to different oligosaccharides and plays a role in antigen capture and cell adhesion. CD209 also functions as a receptor for many bacterial, fungal and viral pathogens. In B cells, CD209 expression enhances infections by HHV8 and H5N1 viruses and in HIV positive patients, promotes trans-infection of CD4+ T cells. Besides its role in cell adhesion and pathogen recognition, the role of CD209 in B cell physiology remains elusive. Our goal is to identify and characterize CD209-induced signaling pathways in human B cells and determine how these pathways relate to normal and pathologic B cell responses. Our data shows that CD209+ lymphoblastic B cells have a higher level of basal cell death suggesting that expression sensitizes B cells to apoptosis. Stimulating CD209+ B cells using an anti-CD209 antibody or Mannan, promotes cell survival. Moreover, CD209 stimulation inhibits BCR-mediated programmed cell death and modifies the expression of several genes involved in cell survival and apoptosis (e.g. Bim, BclXL, Xiap). Elucidating the role of CD209 in B cell physiology will have important implications towards understanding the development of the humoral immune response to pathogens such as HHV8, Zika, Dengue and HIV. Moreover, our results will set the groundwork for future studies on vaccine development and biomarker discovery. Supported by NIGMS-INBRE P20 GM103475-14