If I had to use a 22 LR for self defense, I'd go with the 40 gr bullets -- CCI mini-mags or Federal HV -- processed through the Paco Kelly accurizer. The flattened cup shape will give good penetration and still create a crush channel.

Another choice might be the Aguila Interceptor. I haven't tested it as thoroughly as the CCI or Federal but it is just as accurate even though it smells funny