Characterization of T-Dependent and T-Independent B Cell Responses to a Virus-like Particle

Natural pathogens, such as viruses, often induce T-dependent and T-independent Ab responses. However, the activation and differentiation of Ag-specific B cells under these conditions had not been examined in detail. In this study, we used bacterial phage Qβ-derived virus-like particles (Qβ-VLPs) as an immunogen to examine the T-independent and T-dependent phases of the response in mice. Using Qβ-specific cell labeling and enrichment methods developed in this study, we were able to characterize the rare Ag-specific B cells in detail. Surprisingly, we found that Qβ-VLPs could induce Bcl-6 expression in pregerminal center B cells independently of T cell help. In addition, Qβ-VLP-induced T-independent responses could lead to isotype-switched and somatically mutated memory B cells. Finally, in contrast to what has been reported with several other Ags, long-lived IgG⁺ memory cells were induced by Qβ-VLPs, with IgM⁺ memory B cells being produced but only evident for a limited time, suggesting that different types of immunogens may preferentially generate or maintain IgM⁺ versus IgG⁺ memory B cells.