I've skimmed through the comments and a few have said an SR22. I have one, it's okay, but I have had some feed issues with it with certain ammo and a few failures to fire, but those almost always shot on the DA second strike.
I really can't recommend any semi-auto .22 pistol though because there's no marketed .22 LR self defense ammunition and I think if ammo makers came out with .22 LR defense ammo that had a hyper velocity with good, reliable rimfire priming in them, a bullet that was made to penetrate as deep as possible with the little .22 it would sell very well. Even if it cost $20 for a 50 round box, people would pay for it like they do with the short barrel .22 Mag JHP.
I digress, I would either look at a .25 ACP or a .32 revolver. Used Beretta 950's are still available and at decent prices and they hold 8 rounds in a mag. You can get .25 FMJ for under $15 per 50 rds online and imo, FMJ is the only .25 to use for defense and most reliable feeding.
As for .32 revolvers, there's the Charter Arms, but it's only a 5 shot and I hate 5 shot .32 H&R Mag revolvers. Charter did make 6 shot .32 S&W Long revolvers way back and you can find them on gunbroker for $250 occasionally. The triggers on the older Charters are really, really smooth and nice. Besides Charters, Ruger LCR in .327 and give her a box of .32 S&W Long, which you can find online for under $17 per 50 rds.