If you use Exchange Online Protection (EOP) and have a third party service in front of Office 365, rate limits may be applied to your SpamTitan IP address(es) on Office 365 mail servers, as these IPs are new to Microsoft and do not yet have a reputation.

When rate limits are applied, all email exceeding the allowed rate is temporarily rejected. Rejected emails are sent to the deferred queue with the reply 451 5.7.(500-699) Server Busy. Please try again later.

A solution is to set up a connector to apply security restrictions to email sent from your partner organization (or on-premise device) to Office 365. See Set up a connector to apply security restrictions to mail sent from your partner organization to Office 365 .