![]() It is noteworthy that the fate of the large number of plasmablasts present in circulation at the peak of the plasmablast wave has never been quantitatively followed although it is well established that the majority apoptose and only a relatively small fraction mature to long lived plasma cells and are able to take residence in niches so that they can contribute to serological memory. ![]() Plasmablast bursts following vaccine or infection are accompanied by a dramatic increase in the antigen-specific antibody titer but generally seem to have little impact on the total concentration of immunoglobulin in blood. The level of IgG produced by long-lived plasma cells changes very slowly over time. For example, the Immunoglopbulin G (IgG) concentration in healthy adults is maintained at roughly between 7–17 mg/ml. The antibody concentration in blood is homeostatically controlled. The relative contribution of antibodies from long-lived plasma cells, transient plasmablasts and by “natural antibody”-producing cells (rodent B1 and marginal zone B cells, and perhaps the human analogues of B1 cells, although these have yet to definitively identified) to the serological immunity is poorly understood. A third component is contributed by natural antibodies which recognize common pathogen antigens such as galactose- α-1,3-galactose (Anti-Gal) and have an innate-like protective function. The compendium of antibodies produced first by long-lived plasma cells and second by transient waves of short-lived plasma cells or plasmablasts (elicited in response to pathogen, vaccine or autoantigen stimulation) constitutes the two main components of antibody serological immunity. Of note, a fraction of bone marrow plasma cells have been recently reported to lack CD19 expression and to be protected from mobilization and replacement by newly formed antibody producing cells following infection, underscoring the heterogeneity of the long-lived compartment of plasma cells and, by extension, the pool of serum immunoglobulins. Long-lived plasma cells reside predominantly but not exclusively in the bone marrow, surviving within specialized anatomical niches with the help of anti-apoptotic signals provided by stromal cells. We now know that long-lived plasma cells constitute the (most likely) irreversible end-point of B cell development, show little or no evidence of proliferation and produce copious amounts of antibodies for years, and quite possibly for decades, in humans. This latest discovery coincided with the development of new technologies in protein chemistry and the advent of molecular biology that, together, catalyzed a remarkable pace of progress in the understanding of B cell development and antibody formation. It was another decade before the plasma cell, which is responsible for the secretion of antibodies, was discovered, and then it was only 50 years ago, in 1965 that it was convincingly shown that antibodies are produced by B lymphocytes. But it would take Landsteiner until the twilight of his career to formally demonstrate that an anti-serum does not comprise merely a single antibody but rather a mixture of different antibody populations of unknown complexity. The genesis of serology dates to the end of the 19 th century and the pioneering “serum therapy” of Emil von Behring and Paul Ehrlich, followed for decades by elegant studies on the specificity of serological reactions by Karl Landsteiner. Serology is classically defined as the study of proteins, predominantly antibodies, found in blood and secretions such as saliva. Additionally, these technologies also hold great promise for therapeutic antibody and biomarker discovery in a variety of settings In parallel, the advent of high throughput methods for antigen and immunosignature discovery opens up unprecedented opportunities to transform our understanding of numerous key questions in adaptive humoral immunity, including the nature and dynamics of serological memory, the role of polyspecific antibodies in health and disease and how protective responses to infections or vaccine challenge arise. Thanks to very recent technology advancements it is now becoming possible to identify and quantify the individual antibodies comprising the serological repertoire. The antibody repertoire is shaped by the historical record of exposure to exogenous factors such as pathogens and vaccines, as well as by endogenous host-intrinsic factors such as genetics, self-antigens, and age. The ensemble of antibodies found in serum and secretions represents the key adaptive component of B-cell mediated humoral immunity.
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