If you are an Exchange Online Protection (EOP) user and you have a 3rd party service in front of Office 365 rate-limits may be applied to your SpamTitan server IP address/es on the Office 365 mail servers.  This is due to the fact that these IP’s are new to Microsoft and do not yet have a reputation. 

When rate limits are applied all mail exceeding the allowed rate will be temporarily rejected.  The rejected mails will end up in the deferred queue with the reply "451 5.7.(500-699) Server Busy. Please try again later".  This relates to Office 365 IP throttling.

The solution to fix this would be to setup a connector to apply security restrictions to mail sent from your partner organization (or on-premise device) to Office 365. Please find the detailed solution in the following KB article: