Monoclonal antibodies (mAbs) are the most promising and dominant class of biotherapeutics, due to the strategical combination of their targeting power with diverse effector functions. Here, we present the immunogenomic engineering of a murine hybridoma cell line to generate a Plug-and-(dis)play (PnP) platform for the expression of recombinant antibodies. Taking advantage of the cutting-edge CRISPR-Cas9 genome editing technology, we used homology directed repair (HDR) to exchange the endogenous variable heavy chain (VH) with a fluorescent reporter, mRuby, and concomitantly deleted the VL by non-homologous end joining (NHEJ): this starting platform cell line could be subsequently reprogrammed through the precise integration of a synthetic antibody scaffold, ultimately leading to full-length antibody surface expression and secretion following a protocol cheaper and more streamlined than conventional generation of stable cell lines. The additional value of the platform was confirmed by exchanging the murine heavy constant region with the human one, which enabled the expression of fully human antibodies, and providing a proof-of-principle for a novel selection system for cells expressing non-Ig recombinant proteins: relevant proteins, like vaccine antigens, can be expressed from a transgene that restores a knocked-out version of mRuby, allowing selection by flow cytometry. The typical antibody engineering workflow is composed of several steps, many of them relying on microbial expression hosts due to the necessity of a higher throughput. However, this aspect can result in the isolation of clones that would not necessarily perform optimally when expressed as full-length IgG. Integrating mammalian expression as a more consistent part of the discovery process would facilitate the isolation and optimization of better antibody therapeutics. To explore the power of the PnP platform as a discovery and engineering tool, we established an assay for the screening of VL-only immune libraries combined with a single VH of interest. Such a concept will pave the way for a more comprehensive full-length immune library display, that will possibly lead to a faster and more efficient workflow for the isolation of novel binders compared to traditional hybridoma generation. An improved HDR donor plasmid allowed to reach a 5 to 10-fold higher HDR efficiency of library integration (5%) and, consequently, significantly better display throughput. The potential of this optimized workflow was exemplified by the successful screening of a random mutagenesis library that, by focusing exclusively on the VH region, led to affinity maturation and isolation of variants with a 4-fold improvement over an already existing high affinity clone. Notably, this positive result was reached with a library size in the 10^4 range. In this context, library screening was assisted by next-generation sequencing (NGS), which effectively complemented the process by recovering additional sequences that could be explored, and providing insight into library diversity and dynamics during enrichment. In conclusion, we think that the PnP platform can offer a useful tool for small scale antibody expression and production, particularly valuable for research labs, and a screening platform that effectively combines the advantages of mammalian display with the efficiency and convenience of precision genome editing, finally allowing the discovery and engineering of recombinant antibodies of synthetic and natural origin.