Plasma cell formation, secretion, and persistence: the short and the long of it.

B cells can be activated by cognate antigen, anti-B-cell receptor antibody, complement receptors, or polyclonal stimulators like lipopolysaccharide; the overall result is a large shift in RNA processing to the secretory-specific form of immunoglobulin (Ig) heavy chain mRNA and an upregulation of Igh mRNA amounts. Associated with this shift is the large-scale induction of Ig protein synthesis and the unfolded protein response to accommodate the massive quantity of secretory Ig that results. Stimulation to secretion also produces major structural accommodations and stress, with extensive generation of endoplasmic reticulum and Golgi as part of the cellular architecture. Reactive oxygen species can lead to either activation or apoptosis based on context and the high or low oxygen tension surrounding the cells. Transcription elongation factor ELL2 plays an important role in the induction of Ig secretory mRNA production, the unfolded protein response, and gene expression during hypoxia. After antigen stimulation, activated B cells from either the marginal zones or follicles can produce short-lived antibody secreting cells; it is not clear whether cells from both locations can become long-lived plasma cells. Autophagy is necessary for plasma cell long-term survival through the elimination of some of the accumulated damage to the ER from producing so much protein. Survival signals from the bone marrow stromal cells also contribute to plasma cell longevity, with BCMA serving a potentially unique survival role. Integrating the various information pathways converging on the plasma cell is crucial to the development of their long-lived, productive immune response.