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. Plasmablasts are the precursors of the cells that produce antibodies, which are necessary to fight infections but which can also cause disease when produced inappropriately. Plasmablasts are generated in a normal immune response, but the mechanisms driving this response are poorly defined in humans. Plasmablasts are produced abnormally in systemic lupus erythematosus (SLE). SLE is also associated with increased levels of BLyS and type-1 interferons (IFN-I), which may induce plasmablast differentiation. Whether increases in serum BLyS or IFN-1 are detectable in a normal immune response, as opposed to the abnormal, autoimmune response in SLE, is unknown. The primary goal of this study is to determine whether increases in BLyS or IFN-1 are detectable in the blood during a normal immune response in healthy individuals. This preliminary study, completed in year 1, used the GCRC to administer pneumovax to 10 healthy subjects. Blood samples will be taken at days 0, 3, 6, and 9. Dr. Carter used the samples to study plasmablasts, IFN-1 and BLyS. The preliminary study demonstrated an increase in serum IFN-1 in normal immune response. This information will be used to study a second cohort of 15 healthy subjects and 15 with lupus, to define the variabilty in BLyS and IFN-1 responses in normal immune responses between healthy individuals and those with lupus. This will determine whether the increase in BLyS and/or IFN- 1 are inherently greater in SLE patients, a potential mechanism for this disease.
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