Rabbit Monoclonal Antibodies

Rabbit monoclonal antibodies are reliable and highly specific alternatives to mouse monoclonal antibodies. Benefitting from the high reproducibility of all monoclonal antibodies, rabbit monoclonal antibodies further demonstrate the natural advantages of the rabbit immune system, which is able to produce a more diverse repertoire of antibodies of higher affinity and specificity than their rodent counterparts. Rabbit monoclonal antibodies can be produced using traditional hybridomas or with recombinant DNA technology as recombinant antibodies, and have found extensive use in research and diagnostics in applications such as IHC, ICC/IF, western blot, ELISA and flow cytometry.

We offer over 5,500 high specificity rabbit monoclonal primary antibodies.

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Advantages of Rabbit Monoclonal Antibodies

Monoclonal antibodies have traditionally been generated using mouse cells. While mouse is still the most common host species, monoclonal antibodies are now available from a variety of host species including rats (XYZ LINK), hamsters (XYZ LINK), and rabbits.

Rabbits have been used for decades as a source of polyclonal antibodies, which are heterogeneous collections of antibodies binding to multiple epitopes on an antigen. The greater specificity granted by all monoclonal antibodies, which bind to a single epitope, can result in increased reproducibility and reduced background signal, and has expanded the application of antibodies into therapeutic avenues.

Compared to mouse monoclonal antibodies, rabbit monoclonal antibodies:

Consistently show higher specificity and greater affinity (possible to attain picomolar range of K_D = 10^-12)
Recognize a more diverse range of epitopes including on human antigens, increasing the total number of epitopes that can be targeted
Are raised more easily against small molecules such as haptens, producing a higher proportion of antibodies recognizing the small molecule rather than a carrier like KLH
Can be generated against rodent antigens, thanks to the robust immune response of rabbits against rodent immunogens
Are useful in research using mouse models, which are commonly employed but rarely compatible with mouse monoclonal antibodies due to high background signal
Can be better for studying non-protein antigens including lipids, carbohydrates and glycolipids

Recombinant Rabbit Monoclonal Antibodies

Recombinant antibodies show even greater reproducibility than traditional monoclonal antibodies, produced in vitro using recombinant DNA technology. Recombinant rabbit monoclonal antibodies are produced by transfecting cellular expression systems with rabbit heavy and light chain immunoglobulin DNA sequences to produce highly consistent antibodies that are suitable for a wide range of applications. By carefully choosing the combination of light and heavy chain sequences, recombinant rabbit monoclonal antibodies can be precisely controlled and optimized for the highest possible binding efficiency and specificity. Furthermore, the cell drift that can occur in traditional monoclonal antibodies is completely eliminated.

More than 2,600 of our rabbit monoclonal antibodies are produced using recombinant methods.

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Rabbit Antibody Diversity

Rabbits produce a more diverse range of antibodies than mice due to fundamental differences in antibody development, maturation, and epitope recognition, as illustrated in Table 1.

	Rabbit	Mouse
Antibody maturation	Somatic gene conversion and somatic hypermutation	Somatic hypermutation only
Immunodominance	Recognize more epitopes on an antigen; less immunodominance	More immunodominance: most antibodies target select few epitopes
Small molecule recognition	Ability to recognize small peptides, haptens etc.	Difficult to raise antibodies against small molecules
IgG:IgM ratio	Rabbits have a higher IgG:IgM ratio. IgG are more specific	Lower ratio
Complementarity determining regions (CDRs)	Longer, more heterogeneous, so more scope for sequence variation	Shorter
CD1 isotypes for lipid and glycolipid presentation	More CD1 isotypes: CD1a1, CD1a2, CD1b, CD1d, CD1e	Only CD1d
Size	Rabbits are larger animals (~2.5 kg), so up to 50 times more B cells can be isolated from them	Mice are smaller (~25 g)
Inbred strains	Laboratory rabbit strains tend to be less inbred, resulting in more diverse immune responses	Laboratory mice are highly inbred

Table 1: Key features of antibody generation in rabbits and mice

The consequence of the features outlined in Table 1 is that a larger pool of more diverse antibodies are generated in rabbits, increasing the overall likelihood that a highly specific, high affinity antibody will be found.

Somatic Hypermutation and Somatic Gene Conversion

Somatic hypermutation (SHM) and somatic gene conversion (SGC) are two mechanisms for increasing the variability of antigen recognition sites in antibodies. SHM introduces point mutations to the variable regions of immunoglobulin genes in B cells after the initial antigen exposure, resulting in even higher affinity antibodies. SGC refers to replacing stretches of DNA that code for antibody variable regions with fragments of non-utilized variable domains of pseudogenes. While SHM is common across many species, SGC is predominantly only used in chickens and rabbit immunoglobulin gene diversification.

More detail on antibody maturation can be found in our guide on Antibodies in the Immune System.

Rabbit Monoclonal Antibody Production

The first method for producing large amounts of antibody of a predefined specificity, monoclonal antibodies, was developed by Köhler and Milstein in the 1970s (Figure 1). It was not until 1995 when the first plasmacytoma cells of rabbit origin, 240E-1 cells, were created via transgenic manipulation to act as fusion partners for rabbit B cells to produce stable rabbit hybridomas.

Schematic of how to generate monoclonal antibodies

Figure 1: Monoclonal antibody production in rabbits and mice. B cells from an immunized animal are taken and fused with myeloma cells to form hybridomas, a stable cell that produced antibodies that targeted a single epitope on the immunogen. Successfully fused hybridomas are isolated by culturing them in hypoxanthine aminopterin thymidine (HAT) medium for up to 2 weeks. These culture conditions removed myeloma cells due to their lack of expression of the hypoxanthine guanine phosphoribosyltransferase enzyme (necessary for growth in HAT medium), while unfused B cells have a short lifespan. The surviving hybridoma cells are then clonally selected and screened to isolate the clones that produce the best antibodies for a given application.

Rabbit Monoclonal Antibody Applications

Rabbit monoclonal primary antibodies can be applied to all of the same techniques as other monoclonal antibodies, including western blot, IHC, ICC/IF, ELISA, ChIP and flow cytometry. When working with mouse tissue, which is prevalent in basic and preclinical research, using monoclonal antibodies from rabbit avoids the mouse-on-mouse background issues that often beset these applications.

Despite monoclonal antibodies being commonly used as treatments of human disease, there are currently no FDA-approved rabbit monoclonal antibodies for therapeutic uses, although some are in clinical trials, such as sevacizumab (anti-VEGF) and APX005M (anti-CD40). As diagnostic tools, there are at least 11 rabbit monoclonal antibodies currently available. The majority of these detect tumor-associated antigens, including HER2 (such as Roche’s anti-HER2 [4B5] clone), estrogen receptor, and PD-L1.