Journal
VACCINE
Volume 31, Issue 44, Pages 5088-5098Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2013.08.055
Keywords
B-cells; Lentiviral VLP; T-independent activation
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Funding
- Deutsche Forschungsgemeinschaft [TRR60]
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In animal models, lentiviral particles (LP) were shown to be promising HIV vaccine candidates. Since little is known about the direct impact of LP on antigen-specific B cells, we incorporated Hen Egg Lysozyme (HEL) into LP (HEL-LP) derived from HIV to study their effect on HEL-specific, B cell receptor-transgenic B-cells (HEL+B-cells) in vitro. We observed preferential binding of HEL-LP to HEL+B-cells and their efficient internalization. HEL-LP were able to effectively cross-link B-cell receptors as indicated by the loss of surface CD62L. In the absence of CD4(+) T-cells, other activation events induced by LP in cognate naive B-cells included increased expression of activation and co-stimulatory molecules as well as an enhanced proliferative response. Additionally, the B-cell phenotype shifted toward a germinal center pattern with further differentiation into memory and IgG3- and IgA-producing cells. The observed CD4(+) T-cell independent activation and differentiation may be due to LP-induced expression of CD40L by a subset of cognate B-cells. Thus, even in the absence of CD4(+) T-cells LP provide strong direct activation signals to cognate naive B-cells, which may contribute to the strong humoral immune responses observed after LP immunization. (C) 2013 Elsevier Ltd. All rights reserved.
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