Publications (2)40.27 Total impact
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Article: Rapid cloning of high-affinity human monoclonal antibodies against influenza virus.
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ABSTRACT: Pre-existing neutralizing antibody provides the first line of defence against pathogens in general. For influenza virus, annual vaccinations are given to maintain protective levels of antibody against the currently circulating strains. Here we report that after booster vaccination there was a rapid and robust influenza-specific IgG+ antibody-secreting plasma cell (ASC) response that peaked at approximately day 7 and accounted for up to 6% of peripheral blood B cells. These ASCs could be distinguished from influenza-specific IgG+ memory B cells that peaked 14-21 days after vaccination and averaged 1% of all B cells. Importantly, as much as 80% of ASCs purified at the peak of the response were influenza specific. This ASC response was characterized by a highly restricted B-cell receptor (BCR) repertoire that in some donors was dominated by only a few B-cell clones. This pauci-clonal response, however, showed extensive intraclonal diversification from accumulated somatic mutations. We used the immunoglobulin variable regions isolated from sorted single ASCs to produce over 50 human monoclonal antibodies (mAbs) that bound to the three influenza vaccine strains with high affinity. This strategy demonstrates that we can generate multiple high-affinity mAbs from humans within a month after vaccination. The panel of influenza-virus-specific human mAbs allowed us to address the issue of original antigenic sin (OAS): the phenomenon where the induced antibody shows higher affinity to a previously encountered influenza virus strain compared with the virus strain present in the vaccine. However, we found that most of the influenza-virus-specific mAbs showed the highest affinity for the current vaccine strain. Thus, OAS does not seem to be a common occurrence in normal, healthy adults receiving influenza vaccination.Nature 06/2008; 453(7195):667-71. · 36.28 Impact Factor -
Article: Presence of p16 hypermethylation and Epstein-Barr virus infection in transplant-associated hematolymphoid neoplasm of the skin.
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ABSTRACT: Epstein-Barr virus (EBV) is associated with the malignant transformation of B, T, and NK lymphocytes in humans, especially in immunosuppressed individuals. We describe an unusual case confined to the skin in a 39-year-old African American female following a renal transplant. Morphologically and immunophenotypically, the tumor was best classified as a plasmablastic lymphoma; however, the neoplastic population revealed rearrangements of both immunoglobulin heavy chain (IgG) and T cell receptor gamma (TCR-gamma). In situ hybridization demonstrated the presence of Epstein-Barr early RNA species (EBER) in the lymphoma cells, consistent with EBV infection. We have previously demonstrated that EBV-induced reactive oxygen is associated with hypermethylation of the tumor suppressor gene p16 in Burkitt lymphoma, and that p16 hypermethylation is nearly always associated with EBV infection in Burkitt lymphoma. Further studies are needed to determine whether p16 is widely suppressed in immunosuppression-induced lymphoma. In this study, we demonstrated high levels of hypermethylation of the tumor suppressor gene p16, thus supporting the role of EBV as a carcinogen in post-transplant lymphoproliferative disease.Journal of the American Academy of Dermatology 12/2006; 55(5):794-8. · 3.99 Impact Factor
