Chapter 7 - Induction and Regulation of Mucosal Memory B Cell Responses

Abstract

Memory B cells develop after mucosal vaccination, but little is known about how and where these cells are induced and maintained for long periods of time. The gut immune system is best characterized for its ability to generate memory B cells, but the respiratory and genital tracts can also respond with memory B cell development. Most memory B cells are formed in germinal centers (GCs) located in the organized immune inductive sites, such as the Peyer’s patches (PPs) in the small intestine. Specific markers can be used to trace memory B cells in both humans and mice, and techniques to characterize these cells at the single-cell level are being investigated. Experimental models as well as human studies have identified that not only isotype-switched memory B cells but also IgM+ memory B cells arise after mucosal immunization. The PPs are the prime sites for gut mucosal memory B cell stimulation and also the sites where most quiescent IgA+ memory B cells reside. Some additional markers that can be used to identify memory B cells are CD80, PD-L2, and CD73 in mice and CD27 in humans. Upon reactivation, mucosal memory B cells expand in secondary GCs and undergo strong affinity selection and isotype-switching to become IgA plasma cells that populate the lamina propria. From a clonal perspective, memory B cells appear less mutated and poorly related to long-lived plasma cells, but after reactivation, responding memory B cells acquire more mutations and are now closely related to IgA plasma cells. There is growing interest in identifying biomarkers that can be used to assess the memory B cell potential in a given vaccine. For example, it was suggested that serum CXCL13 levels after vaccination could correlate to memory B cell differentiation. With the rapid development of new technologies, the future looks bright in terms of our ability to develop better and more efficacious vaccines with a strong memory B cell stimulating function. This work will likely depend on the next generation of safe yet effective mucosal vaccine adjuvants.