Interplay of different TLR signaling pathways and the affect of simultaneous stimulation of TLR and BCR on B lymphocyte activation

Authors

• BP Theall
• TA Henke
• SK Pierce
• M Akkaya

Abstract

B cells are the key components of the humoral immune response due to their ability to produce specific antibodies in response to foreign antigens. Although B cells are primarily activated through their recombinant cell surface B cell receptors, they can also be activated via various pattern recognition receptors such as Toll like receptors (TLRs) in an antigen independent fashion. These germline-encoded receptors when stimulated, can trigger a cascade of signaling events leading to survival, cytokine production, and proliferation. Two main signaling adapters, namely MyD88 and TRIF, are responsible for transmission of the TLR stimulus into various intracellular pathways. While TLR4 can engage with both MyD88 and TRIF, TLR3 and TLR9 exclusively pair with TRIF and MyD88 respectively. Here we set out to investigate the interplay between TLRs utilizing different signaling pathways as well as how simultaneous stimulation of TLRs and BCR affect the functionality of B cells. Our findings identified both synergistic and antagonistic outcomes in various B cell responses such as proliferation, cell surface marker expression, antigen processing, presentation, and antibody production. Using knock outs of MyD88 and TRIF, we also revealed the relative contribution of these signaling pathways and that absence of one might indirectly affect the functioning of the other. These results further understanding of the complex TLR signaling machinery in B lymphocytes.

Scientific Focus Area: Immunology

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