Polyclonal vs Monoclonal Antibodies (Part 1- mAbs)
Welcome to the 1st part of the 19-part series on monoclonal antibodies (mAbs).
Polyclonal antibodies
B lymphocytes often referred to as B cells, produce antibodies. The origin and maturation of B cells occur in the bone marrow. Then, these mature naive B cells are released into the blood, and they keep recirculating between the lymph, blood, and secondary lymphoid tissues. The B cells have specific receptors on their membrane for antigen recognition. These receptors are called B-cell receptors or BCRs, composed of membrane-bound immunoglobulins and a heterodimer Ig-α/Ig-β held together by a disulfide bond.
Every day about 1 billion cells are produced in our body. The BCRs present have pre-existing specificities, because of which B cells can recognize and react to almost any possible antigen they encounter. Each B cell has around 100,000 BCRs on its surface. The important point is that all these BCRs of one B cell are specific for only one particular epitope on an antigen.
When a mature B cell encounters an antigen, it gets activated and proliferates into a large clone of B cells. Some of them differentiate into antibody-producing plasma cells, and others become long-lived memory B cells. These plasma cells and memory cells are specific to the antigen, or more specifically, the antigen’s epitope, which the mature B cell initially encountered. These are the sequences of events that lead to the production of antibodies.
Assume a bacterial cell invaded the body. The bacterial cell membrane contains many molecules like polysaccharides, lipopolysaccharides, proteins, etc., and these molecules vary in their chemical nature. These molecules of bacteria are recognized as foreign by the B cell receptors. Or in other words, the bacterial cell is the antigen, and the bacterial cell molecules are the epitopes to which the B cells bind via their B cell receptors. B cells of diverse specificities circulating in the body recognize the different bacterial cell membrane molecules.
For ease of understanding, suppose four types of B cells are circulating in the body, with different specificities. Each of these B cells is specific for a single epitope on an antigen; in our case, the antigen is a bacterial cell. So, when there is an invasion by the bacterial cell, these B cells recognize and bind to the specific epitopes on the antigen and get activated. Each of these B cells then proliferates and produces a large clone of cells.
Some of the activated B cells in each case get differentiated into antibody-producing plasma cells. And each of the plasma cells secretes antibodies specific to the epitope, which triggered their differentiation.
So, as a result, our immune system produces four types of antibodies for the antigen bacterial cell, each type specific for a different epitope. Antibodies derived from multiple B cell clones are called polyclonal antibodies. In other words, polyclonal antibodies are the heterogeneous mixture of antibodies, each recognizing a different epitope on the same antigen.
Monoclonal antibodies
Now let’s discuss monoclonal antibodies (often referred to as mAbs) that have revolutionized the treatments for several severe conditions like cancer, arthritis, autoimmune diseases, etc. Most antigens have multiple epitopes; therefore, they induce the proliferation and differentiation of various B cell clones. Each clone is derived from a B cell that recognizes a particular epitope. When an antigen binds to a specific B cell, it stimulates it to divide into a clone of cells that have the same antigen specificity as that of the parent B cell.
Like in above Fig, clone 1 of B cells is derived from a B cell that can recognize epitope 1 of the Ag. And clone 2 of B cells is derived from B cell that can recognize epitope 2 of the Ag and so on. Therefore, if the antibodies are raised against all the four epitopes of antigen, then the resulting serum antibodies are heterogeneous, comprising a mixture of antibodies, each specific for one epitope. These heterogeneous antibodies are called polyclonal antibodies.
On the other hand, the monoclonal antibodies, as the name indicates, are the antibodies that are derived from the clones of a single activated B cell that recognizes a particular epitope.
Thus, the monoclonal antibodies recognize a single specific epitope on an antigen. In other words, monoclonal antibodies are identical antibodies with the same antigen specificity. Monoclonal antibodies have enormous applications for research, diagnostic and therapeutic purposes. Though polyclonal Abs facilitate phagocytosis and lysis of pathogens in vivo. But unfortunately, Ab heterogeneity that increases immune protection in vivo often reduces the efficacy of an antiserum for various in vitro purposes. Therefore, for research and diagnostic purposes, monoclonal antibodies that are specific for a single epitope are preferable.
If you liked this article and want to know more about Antibodies and their role in Therapeutics and Diagnosis, click the below links.
For book lovers:
For video lovers:
Happy learning!
