The rabbit immune system generates antibody diversity and optimizes affinity by mechanisms different from those of mice and other rodents. Compared with traditional mouse mAbs, the rabbit mAbs have advantages in diagnostics with high affinity and specificity toward antigens, more diverse epitope recognition, and greatly improved response to small-size epitopes and mouse antigens. The rabbit immunoglobulin heavy chain (IGH) locus contains over 200 IGH variable germline genes, with over 50% have been found to be “non-functional”. Also, more than 50 IG Kappa V and 17 IG Lambda V functional genes were identified with genomic sequencing (IMGT database). The diversity of rabbit VH repertoire is more limited, and the V light (VL) repertoire is more diverse than that in mice and humans. Most rabbit antibodies are derived from the IGHV1 gene. In addition, the rabbit VL repertoire displays a larger complementarity-determining region (CDR)-L3 loop length than its human and mouse counterparts. Rabbit serum and plasma samples contain around 10 mg/ml of IgG. The use of hybridoma technology or other platforms (e.g., phase display, single B cell antibody technology) for the production of rabbit monoclonal antibodies has created the requirement for a fast and simple procedure for quantifying antibody production.
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