550 5.7.750: client blocked from sending from unregistered domain

Microsoft says this NDR is typically generated when a large volume of email is sent from a domain that isn't an accepted domain in your organization. Microsoft 365 only allows a certain amount of mail to be sent from an unregistered (unaccepted) domain. Its NDR reference describes the trigger as a suspicious number of messages from unprovisioned domains coming from the tenant.

The NDR goes to your own users. It's Microsoft 365 refusing to send your outbound mail, not a recipient refusing it. Common ways to get here: an application, scanner, website or on-premises server relays mail through Microsoft 365 with a From address in a domain you never added; a domain was removed from the tenant but something still sends as it; or a connector is set up wrongly, which Microsoft names as a less common cause.

There's also a security angle. Microsoft warns that attackers sometimes create new inbound connectors in organizations to send spam, so check for connectors you don't recognize and for compromised accounts before you ask for the block to be lifted.

Only an email admin can fix this. Microsoft's most common solution is to add and validate every domain you send from. Where mail comes from an on-premises server or another service through a connector, Microsoft recommends a certificate-based outbound connector whose certificate domain is an accepted, validated domain. After you've addressed the cause, contact Microsoft Support to have the block removed.