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To promote such early and robust B cell stimulation, we hypothesized that live RABV-based vaccines directly infect B cells, thereby activating a large pool of antigen-presenting cells (APCs) capable of providing early priming and costimulation to CD4<jats:sup>+<\/jats:sup>T cells. In this report, we show that live RABV-based vaccine vectors efficiently infect naive primary murine and human B cells<jats:italic>ex vivo<\/jats:italic>. Infection of B cells resulted in the significant upregulation of early markers of B cell activation and antigen presentation, including CD69, major histocompatibility complex class II (MHC-II), and CD40 in murine B cells or HLA-DR and CD40 in human B cells compared to mock-infected cells or cells treated with an inactivated RABV-based vaccine. Furthermore, primary B cells infected with a live RABV expressing ovalbumin were able to prime and stimulate naive CD4<jats:sup>+<\/jats:sup>OT-II T cells to proliferate and to secrete interleukin-2 (IL-2), demonstrating a functional consequence of B cell infection and activation by live RABV-based vaccine vectors. We propose that this direct B cell stimulation by live RABV-based vaccines is a potential mechanism underlying their induction of early protective T cell-dependent B cell responses, and that designing live RABV-based vaccines to infect and activate B cells represents a promising strategy to develop a single-dose postexposure rabies vaccine where the generation of early protective antibody titers is critical.<\/jats:p>","DOI":"10.1128\/jvi.00800-13","type":"journal-article","created":{"date-parts":[[2013,6,13]],"date-time":"2013-06-13T03:00:06Z","timestamp":1371092406000},"page":"9097-9110","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["B Cell Infection and Activation by Rabies Virus-Based Vaccines"],"prefix":"10.1128","volume":"87","author":[{"given":"Andrew G.","family":"Lytle","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"James E.","family":"Norton","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corin L.","family":"Dorfmeier","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shixue","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James P.","family":"McGettigan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA"},{"name":"Jefferson Vaccine Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA"},{"name":"Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"1137","volume-title":"Fields virology","author":"Dietzschold B","year":"1996","unstructured":"DietzscholdB RupprechtCE FuZF KoprowskiH. 1996. 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