Virus-like particle vaccine activates conventional B2 cells and promotes B cell differentiation to IgG2a producing plasma cells.
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.
Molecular Surgeon Research Center, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Sheng
S
Zhang
Rafael
R
Cubas
Min
M
Li
Changyi
C
Chen
Qizhi
Q
Yao
D000818:Animals; D000917:Antibody Formation; D018956:CD5 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D018858:Germinal Center / Q000276:immunology; D007114:Immunization; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D051917:Leukosialin / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology*; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D014771:Virion / Q000276:immunology*
D018956:CD5 Antigens; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D051917:Leukosialin; D014765:Viral Vaccines; D017493:Leukocyte Common Antigens