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Mol Immunol. 2009 Jun;46(10):1988-2001. doi: 10.1016/j.molimm.2009.03.008. Epub 2009 Apr 18.

Virus-like particle vaccine activates conventional B2 cells and promotes B cell differentiation to IgG2a producing plasma cells.

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  • 1Molecular Surgeon Research Center, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract

We have previously shown that immunization with SIV-, SHIV-, or HA (influenza hemagglutinin)-virus-like particles (VLPs) elicits a strong humoral immune response in mice. However, little is known about the action VLPs exert on immune effector cells, including B cells. In this study, we found that all three types of VLPs could directly bind and activate B cells in vitro. VLPs stimulated the proliferation of B220(+)IgM(+)CD43(-)CD5(-) B2 cells and their differentiation to plasma cells that preferentially produce IgG2a antibodies. Up-regulation of Blimp-1, XBP-1, IRF4, and AID genes, which are responsible for class-switch recombination and somatic hypermutation, was observed in VLP-activated B2 cells. Stimulation of naïve splenocytes with VLPs led to a high expression of IL-12, RANTES and MIP, the cytokine milieu that favors B cell differentiation into IgG2a secreting cells. VLP immunization of C57BL/6 mice corroborated our in vitro data showing enlarged germinal centers and expanded conventional B2 cells, but no enlarged marginal zone B1 cells, in the spleen. Enhanced antigen-specific plasma cell formation, antibody production, and IgG2a class switching were found in VLP-immunized groups. The current study details the interaction between VLPs and B cells which result in preferential IgG2a antibody production following VLP immunization.

PMID:
19376580
[PubMed - indexed for MEDLINE]
PMCID:
PMC2702656
Free PMC Article

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