Antibody Diversity

Why are antibodies so diverse? This is a question that I found quite challenging on the assessment exam since I have not taken an immunology course. Although I know the background on how an immune response works and I use antibodies for research purposes, I have never learned how antibodies become so diverse. Humans can produce 10¹² different antibodies, but how is this genetically possible when there are not enough genes in the genome to code for that many different antibodies?

Interestingly, all antibodies contain a light and heavy chain; however, the area that makes antibodies so diverse is the antibody binding site. As you can see in the picture there is a variable region in the antibody binding site on the light and heavy chain; these changes are necessary on both chains because a lock and key fit is needed for the antigen to bind to the antibody. This distinct binding site of the antigen is called an epitope; the antibody recognizes this specific site and then binds to it producing the immune response. For research purposes we use antibodies to bind to epitopes of specific proteins, in Western Blotting, and have a secondary antibody bound that has a fluorescent tag; this enables easier detection. Let’s get back to the original question, the genetic event that makes antibodies diverse is DNA rearrangements followed by alternative splicing of the transcripts; this allows humans to produce a million different antibody molecules with a limited genome code. On human chromosome 14 a heavy chain variable domain can be found and on human chromosome 2 and 22 a light chain variable domain can be found. The variable domain is where the DNA rearrangements occur. The domain regions are actually more complicated than that, but this is just a basic description.

Antibodies are a topic of study within themselves, but should a person necessarily know this information. I believe having a basic understanding about an immune response and how binding is a lock and key fit with the antibody and antigen epitope is necessary. Since not all biology students take immunology I think it would be good to talk about this in genetics class, since it would be useful for medical school. There have been many research studies to better understand the diversity of antibodies for molecular assays, for learning about the evolution of antibodies, and for disease understanding along with possible therapies.

For basic information about antibody diversity i read this abstract and introduction since that was all that was available without purchasing. http://www.ncbi.nlm.nih.gov/pubmed/21310488

I also read this research review article called: Antibody Structure, Instability, and Formulation written by Wang et. al., which i found at the AU electron journal center.