Joseph Ashour, PhD
Notwithstanding their antigen specificity, B cells display characteristics of an innate response as well, though their role in the innate response to virus infection has been largely overlooked due to their paucity in vivo. This may be a regrettable omission, given that many infections are recurrent episodes, including those caused by dengue virus (DENV) and influenza virus (IAV) where antigen-specific B-cells are present a priori. Antigen-specific B-cells remain at the site of infection long after the infection has been cleared. Such B-cells express a high affinity pathogen-specific receptor, the BCR, which, upon stimulation, can synergize with the TLR signaling pathway leading to a stronger transcriptional response. In accordance with this, exposure to interferon results in increased TLR7 expression, lowered thresholds for BCR activation and increased cytokine production. Thus for many viral infections, the sentinel role of plasmacytoid dendritic cells (pDCs) might be complemented by antigen-specific B-cells.
The primary focus of the Ashour lab is examining the contribution of antigen-specific B cells to the innate immune response against virus. The tools we use to accomplish this include 1) somatic cell nuclear transfer derived antigen specific B-cells 2) heavy domain of heavy-chain only antibodies isolated from alpacas (nanobodies) and 3) sortase based chemo-enzymatic labeling of host and virus proteins. By combining these cutting edge technologies with conventional biochemistry and cell biology we hope to expand our knowledge in the frontier of virus-B-cell interactions.