How are fully human monoclonal Ab made?

— From transgenic mice (ex: Xenomouse model): — Endogenous mouse Ig (H and L chain) loci are deleted and replaced by human Ig (H and L chain) loci. — After immunization with antigen of interest, somatic fusion is performed resulting in isolation of specific fully human mAbs — From phage display libraries: — Total cDNA of VL and VH gene segments is purified from human B cells — The genes are inserted in tandem in phages that infect bacteria in culture: Billions of different recombinant phages express a random combination of VH and VL (Fab ou Fv fragment) — Phages binding to antigen of interest are amplified in bacterial cultures and resulting antibody fragment is purified