This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human body integrity is largely based on a healthy immune system fighting pathogens. One key feature of the immune system is expression of memory, i.e. maintaining the ability to fight a pathogen upon its re-encounter effectively, even after years of pathogen absence. Based on that, vaccinations can prevent from severe infections. In pathogen defense, proteins binding specifically to the pathogen (antibodies) play a vital role. Antibodies tag the pathogen thus cause highly efficient degradation of the pathogen by specialized immune cells or neutralize it. The physical half-life of antibodies is less than 4 weeks. By contrast, specific antibodies induced by vaccination or infection can be readily detected in human blood serum after decades of antigen absence (humoral memory). This suggests that serum antibody levels are regulated at the stage of antibodysecreting cells, and their specific precursors (memory B cells). For both cell types, longevity vs. continuous renewal is discussed as means to maintain the entire cell population and its composition, but both concepts were neither proven nor disproven physically. In this project, want to measure 14C content in the DNA of antibody-secreting cells and memory B cells obtained from donors exposed to elevated levels of atmospheric 14C in Europe during the 1960ies. Elevated levels of the 14C isotope can still be detected in cells being quiescent since then, revealing their age. 14C analysis will require accelerator mass spectrometry (AMS) ensuring a precise quantitation of very low levels of 14C from minimum DNA samples. In analogy to Spalding et al (Cell, Vol. 122, 133?143, July 15, 2005), this analysis will determine the in vivo age of candidate subsets of antibody-secreting cells and memory B cells and prove or disprove longevity of these cells, arguing in favor or against B cell longevity as a key element of humoral memory. The expected results will define new requirements for the successful development of effective vaccines.
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