B-cell activating factor (BAFF) promotes CpG ODN-induced B cell activation and proliferation

• Published in: Cellular immunology 2011, Vol.271 (1), p.16-28
• Main Authors: Buchanan, Rachelle M., Popowych, Yurij, Arsic, Natasha, Townsend, Hugh G.G., Mutwiri, George K., Potter, Andrew A., Babiuk, Lorne A., Griebel, Philip J., Wilson, Heather L.
• Format: Article
• Language: English
• Subjects: Animals; B cell; B-Cell Activating Factor - genetics; B-Cell Activating Factor - immunology; B-Cell Activating Factor - pharmacology; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; BAFF; Bovine; Cattle; Cell Proliferation - drug effects; Cells, Cultured; Coculture Techniques; Drug Synergism; Flow Cytometry; HEK293 Cells; Humans; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lipopolysaccharide Receptors - immunology; Lipopolysaccharide Receptors - metabolism; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Male; Myeloid cells; Myeloid Cells - drug effects; Myeloid Cells - immunology; Myeloid Cells - metabolism; Naive; Oligodeoxyribonucleotides - pharmacology; Receptors, Antigen, B-Cell - immunology; Receptors, Antigen, B-Cell - metabolism; Receptors, Complement 3d - immunology; Receptors, Complement 3d - metabolism; Recombinant Proteins - immunology; Recombinant Proteins - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; TLR9; Toll-Like Receptor 9 - genetics; Toll-Like Receptor 9 - immunology; Toll-Like Receptor 9 - metabolism
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2011.05.016

► B cells activation by CpG ODN is controversial. ► Purified bovine B cells express TLR9 in the absence of B cell receptor engagement. ► CpG ODNs do not promote significant proliferation of highly purified bovine B cells. ► Myeloid cells and/or BAFF significantly increase CpG-specific B cell activation. ► BCR engagement does not augment CpG-specific B cell activation. It is controversial whether naïve B cells are directly activated in response to TLR9 ligand, CpG ODN. Although bovine blood-derived CD21+ B cells express TLR9 and proliferate in response to CpG in mixed-cell populations, purified bovine B cells do not proliferate significantly in response to CpG ODN, even when the B cell receptor is engaged. When co-cultured with CD14+ myeloid cells and/or B-cell activating factor (BAFF), a cytokine produced by activated myeloid cells, there was a significant increase in CpG-specific B cell proliferation, and the number of large B cells in general or positive for CD25, all of which are markers for B cell activation. These data suggest that activated myeloid cells and BAFF prime B cells for significant CpG-specific activation. Understanding the signals required to mediate efficient CpG-induced, antigen-independent and T-cell independent activation of B cells has implications for polyclonal B cell activation and the development of autoimmune diseases.