Rudi Manz

Long-Lived Plasma Cells

Long-term immunological protection depends on the development of memory B cells and antibody-secreting long-lived plasma cells. Antigen activation of B cells and cognate help from T cells initiates a germinal center reaction in which B cells develop into plasma cells secreting high-affinity antibodies. The development of long-lived plasma cells requires interactions between germinal center B cells and T follicular helper cells and within the B lineage a network of interacting transcription factors controls the differentiation process. The newly generated plasma cells leave the peripheral lymphoid organs and home to the bone marrow. CXCL12 produced by the network of reticular stromal cells and signals provided by megakaryocytes and eosinophils are required for plasma cell retention and for their further development into mature long-lived secretory cells. The long-term survival of plasma cells is dependent on the survival factor activation and proliferation induced ligand (APRIL) and eosinophils are a major source of this cytokine. Persisting antibody titers suggest that plasma cells may survive for years during which they continue to secrete large quantities of antibody. The cellular stress associated with the high rate of antibody production may be mitigated by upregulation of the unfolded protein response.