Factors That Regulate the Generation of Antibody-Secreting Plasma Cells

The generation of antigen-specific neutralizing antibodies and memory B cells is one of the most important immune protections of the host and is the basis for successful vaccination strategies. The protective antibodies, secreted by preexisting long-lived plasma cells and reactivated antigen-experienced memory B cells, constitute the main humoral immune defense. Distinct from the primary antibody response, the humoral memory response is generated much faster and with greater magnitude, and it produces antibodies with higher affinity and variable isotypes. Humoral immunity is critically dependent on the germinal center where high-affinity memory B cells and plasma cells are generated. In this chapter, we focus on recent advances in our understanding of the molecular mechanisms that govern fate decision for memory B cells and plasma cells and the mechanisms that maintain the long-lived plasma-cell pool, with emphasis on how the transcription factor Blimp-1 (B lymphocyte-induced maturation protein-1) helps regulate the above-mentioned immunoregulatory steps to ensure the production and maintenance of antibody-secreting plasma cells as well as how it directs memory cell vs plasma-cell fate. We also discuss the molecular basis of Blimp-1 action and how its expression is regulated.