Exploiting human memory B cell heterogeneity for improved vaccine efficacy

Abstract

The major goal in vaccination is establishment of long-term, prophylactic humoral memory to a pathogen. Two major components to long-lived humoral memory are plasma cells for the production of specific immunoglobulin and memory B cells that survey for their specific antigen in the periphery for later affinity maturation, proliferation, and differentiation. The study of human B cell memory has been aided by the discovery of a general marker for B cell memory, expression of CD27; however, new data suggests the existence of CD27⁻ memory B cells as well. These recently described non-canonical memory populations have increasingly pointed to the heterogeneity of the memory compartment. The novel B memory subsets in humans appear to have unique origins, localization, and functions compared to what was considered to be a "classical" memory B cell. In this article, we review the known B cell memory subsets, the establishment of B cell memory in vaccination and infection, and how understanding these newly described subsets can inform vaccine design and disease treatment.

Keywords: B cell; B cell subset; anthrax; antibody; immunoglobulin; influenza; memory B cell; vaccine.

Figure 1

Specifically targeted memory B cell subset versus non-targeted vaccination. (Above) A conceptual cartoon displaying the benefits of designing a vaccination with a particular B memory cell subset targeted. The vaccine would be greatly dependent on the pathogen of interest and route of infection. To prime the most effective B memory subset the type of antigen and adjuvant must be rationally chosen based on the known properties of the subset. By targeting a particular memory B cell subset in a vaccine the localization, type and magnitude of antibody response, and the maintenance of the memory B cell subset populations can be altered to generate an effective antibody response upon subsequent exposure. Conversely, non-specific memory B cell vaccine design can lead to the loss of maintenance and/or establishment of important memory populations, improper response localization, and ineffective antibody response. These factors combined can lead to a loss of efficacy in a vaccine.