IgG molecules

Polyclonal antibodies are preferred by many researchers because they are more versatile than monoclonals. Even their historic issues with variability can be easily addressed.

Contributed by Mike Browning

Many researchers prefer polyclonal antibodies over monoclonals.

In an article in Nature on antibody quality (Monya Baker, Nature  527:545-551, 2015) a paper was cited in which antibodies were used in over 2000 studies. Among these, polyclonal antibodies were used in 1293 studies, and monoclonals were used in 755. This preference for polyclonal antibodies has been echoed in a number of other more recent surveys as well. 

The multiple binding sites available to polyclonals vastly increases their versatility.

What can explain this preference for polyclonal antibodies?  In my opinion, the main reason researchers prefer polyclonal antibodies is that they are more versatile. This versatility can be seen in the ability of polyclonal antibodies to work in a variety of different applications and also in a variety of different species (Stills HF. Polyclonal Antibody Production. Suckow MA, Stevens KA, Wilson RP (Eds). Academic Press, MA, USA, 259–270 (2011). This ability is due precisely to the simple fact that polyclonal antibodies have more binding sites than do monoclonal or recombinant antibodies. If the single binding site of a monoclonal were to be changed by conditions in a new application, then the binding of that antibody would necessarily be lost. In contrast with a polyclonal, the loss of a single binding site would have much less impact given the multiple binding sites available to the poly. A similar logic applies when testing widely divergent species where alterations in the amino acid sequence of a single binding site could lead to the loss of all monoclonal binding. In contrast, such a single alteration would have much less impact due to the multiple binding sites of the poly.

Differences in bleeds has caused variability issues in polyclonal antibodies.

Given the foregoing one might predict that all researchers would prefer polyclonals. However there is one important limitation of polyclonals. This limitation is that polyclonal antibodies show substantial variability between individual bleeds. This variability in the polyclonal antibodies has led many researchers to turn to monoclonal or even recombinant antibodies.

It is possible to minimize polyclonal antibody variability.

Fortunately there is a straightforward solution to the problem of polyclonal antibody variability.  The solution is to pool all the various bleeds of the polyclonal into a single lot from which all subsequent lots will be made. This will eliminate all the lot-to-lot variability of polyclonals. Unfortunately, too few antibody manufacturers follow this simple procedure. However, once they do they will have the most versatile antibody for cross species and cross application usage.

Further Reading

Antibody Variability

Are Monoclonal Antibodies Really More Specific?

1% SDS is the Lysis Buffer of Choice for Most Western Blots

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