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Apparently, with the establishment of the Federal Reserve System in 1913, the nation was divided into twelve Federal Reserve Districts or regions. The districts/regions were determined back in 1913 based on the population numbers at that time. These Federal Reserve Banks distribute the currency to member banks. The letter indicates the bank that distributed the currency into circulation.

There is only one U.S. Bureau of Engraving and Printing, which apparently prints currency for "its customer".
I found this statement at their website:

  • "Packaging Operations is the final stage of the 32-subject currency production process before the currency is shipped to BEP's customer, the Federal Reserve."