1) Go to the BIS web site. Here are the links for the common US providers.
You will see the following (My example is using AT&T)
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You may need to create a new user if this is the first time you are using this. Otherwise proceed to log in
2) You should see a list of email accounts that are accessible from your Blackberry. Click on the Edit icon on the right hand side for the particular email account you want to manage
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3) You can now change the Signature for the email account. Click Save and you are done! Note that you can have different signatures for different email accounts.
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