B Cell Memory and Plasma Cell Development

There are no known specific markers for memory B cells in mice, although studies suggest that the CD38low and CD38high phenotypes are indicative of isotype-switched germinal center (GC) and memory B cells in the mouse, respectively [1]. Further analysis suggested that IgG1+CD38high B cells, but not IgG1+CD38low B cells, are capable of inducing a significant IgG1 secondary response in the adoptive hosts [2], demonstrating that the CD38low and CD38high phenotype distinction can be used to monitor the development of the antigen-specific memory B cells in the T cell-dependent (TD) response. In humans, approximately 30–50% of the peripheral blood B cells are CD27+, and CD27 has been identified as a good surface marker for human memory B cells [3–5]. IgD−CD27+ cells in the peripheral blood have already undergone class switch recombination (CSR) and have accumulated somatic hypermutations (SHMs) in their VH genes in comparison to CD27− B cells, which have not. Polyclonal stimulation of B cells from anthrax vaccine adsorbed (AVA) vaccinated individuals generated AVA-specific IgG+ antibody-secreting cells (ASCs) in vitro, but the deletion of CD27+ B cells abrogated the response [6], indicating that human memory B cells are present in the CD27+ B cell compartment.The immune system memorizes the characteristics of pathogens to provide effective immune protection. Memory B cells and long-lived plasma cells (PCs) account for the long-term humoral immunity elicited by infections and many vaccines. Once generated, memory B cells enter a resting state and persist over long periods of time in the lymphoid organs in the apparent absence of immunizing antigen. T cell-dependent (TD) B cell memory is generated along two fundamentally distinct differentiation pathways. One of these is the classical generation pathway through antibody affinity maturation in the germinal center (GC) reaction with the help of T follicular helper (Tfh) cells. In the other pathway, memory B cells develop in response to a TD antigen before the onset and independently of the GC reaction with the help of T cells other than Tfh. The maintenance of these cells over time may depend on interactions with cells in their environment, perhaps in specialized “niches” akin to those postulated for the maintenance of PCs. Memory B cells provide the quick anamnestic antibody response that follows after antigen reexposure. This activity is critical for eliminating pathogens and toxins that are not efficiently eliminated by preexisting circulating antibodies.Plasma cells are terminally differentiated cells of the B lymphocyte lineage, the cells uniquely able to secrete antibody and thus the cell responsible for antibody-mediated immunity. In addition, because plasma cells can be maintained for extended periods, providing potentially life-long immunity to pathogens and their toxic products, they constitute a crucial component of immune memory. As such, plasma cell biology is fundamental in health in terms of immunity resulting from infection and vaccines. Furthermore, information regarding plasma cell development, differentiation, and survival and the molecular mediators of these processes provides potentially unprecedented insights into plasma cells participating in disease processes such as antibody-mediated autoimmune diseases such as systemic lupus erythematosus and the development of plasma cell cancers such as multiple myeloma.Memory plasma cells residing as mature long-lived plasma cells in bone marrow and inflamed tissues secrete antibodies independently of antigen contact, T cell help and memory B cells and are therefore crucial for maintaining antibody levels. They are refractory to irradiation, immunosuppression and therapies targeting B cells. Consequently, memory plasma cells secreting pathogenic antibodies substantially contribute to the chronicity and therapy resistance of antibody-mediated diseases. Their therapeutic targeting is a promising challenge.