Acceptance With Grace. The best_case scenario__and honestly, the most common reaction__is that your boss will accept your resignation with understanding and sincere congratulations. Your manager will be happy to see that you're advancing your career and moving on to something bigger and better.
Sure, it may sit in the depths of HR until the end of time, but you can be sure of two things: One, your former boss (and future reference) will read it and be impressed. And two, if you ever decide to come back to your company (hey, it happens), it's a very good thing that last thing on file is a great, professionally written resignation letter.