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Polyclonal response is a natural mode of response exhibited by the adaptive immune system. It ensures that a single antigen is recognized by multiple clones of B Lymphocytes.

Mechanism of B cell response

An antigen is any substance (usually a protein) that can be ‘recognized’ by the host organism. As the proteins—polymers of amino acids are very big (at the molecular scale, of course), they cannot be recognized as a whole; instead, certain portions on it—the epitopes are recognized. So, when an antigen is recognized by an antigen presenting cell (APC) like the macrophage or the B lymphocyte, it is broken down into various peptides in the lysosome of that cell following phagocytosis.

The individual peptides are then complexed with major histocompatibility class II (MHC class II) molecules located in the lysosome—exogenous pathway of antigen processing. From here the complex migrates to the plasma membrane, and is elaborated as a complex, which can be recognized by the CD 4+ (T helper cells).

Whatever the cell type, to recognize an antigen or a segment thereof (epitope), requires binding of the antigen with the corresponding paratope present on the receptor present on the surface of the recognizing cell. In the immune system, these are the T (TCR) and the B (BCR) cell receptors. Note that the binding between a paratope and its corresponding antigen is very specific owing to their structures and is guided by various noncovalent bondings not unlike pairing of other types of ligands and their corresponding receptors.

The CD 4+ cells through their TCR recognize the epitope-bound MHC II molecules on the surface of the APCs, and get “activated”. However, complete stimulation requires the B7 molecule present on the APC to bind with CD28 molecule present on the T cell surface close to the TCR. When this activated T cell encounters a B cell with the paratope identical to the one present on its TCR, the latter gets stimulated because of secretion of certain growth factors in a paracrine fashion. However, this activation occurs only when the BCR present on a memory or a naive B cell itself is bound to the corresponding epitope.

This is followed by a manifold proliferation of that particular B lymphocyte, most of the progenies of which terminally differentiate into Plasma or B effector cells, which secrete the antibodies (IgM, and then IgG in that sequence) that have the same paratope as that present on the B and the T cells that had got stimulated initially.

It would do good to highlight again that in the above discussion the BCR, the TCR, and the secreted antibody have an identical paratope that binds to the same epitope.

In the course of this proliferation, the BCR genes can undergo somatic hypermutation making the subsequent encounters with antigens more inclusive in their antigen recognition potential.

Basis of polyclonal response

Polyclonal derives from the words ‘poly’=many and clones. A clone is a group of cells with common ancestry (mother cell).

In natural immune response the memory or naïve B cells exist in only small numbers, which can proliferate upon encountering an antigen to which they are specific. Each such group of cell with identical specificity towards the epitope would be known as a colony or a clone, and would be essentially derived from a common mother cell. Also, the paratopes contained on the antibodies secreted by the derivatives (plasma cells) will be the same.

However, the same epitope can be recognized by naïve/memory cells belonging to different clones. The binding affinities for respective epitope-paratope pairs are varying. The clones that bind to a particular epitope with sufficient strength are “selected” for further proliferation in the germinal centers of the follicles in various lymphoid tissues like the lymph nodes. This is not very different from Darwinian concept of natural selection—a clone that gets selected in one of the encounters stands lesser chance of getting selected if the epitope structure changes somewhat.

Moreover, if the same epitope can elicit response from multiple clones, a single antigen can be broken down into multiple epitopes imparting even greater multiplicity to the overall response.

Significance

• Very apparently, the phenomenon ensures greatest probability of recognizing an antigen.

• It increases the chances of autoimmune reactions through the mechanism of molecular mimicry.

• Monoclonal antibodies have to be produced by a different technique.

See also

• Polyclonal antibodies
• MHC class II
• Antigen processing

References

• Goldsby RA, Kindt TK, Osborne BA and Kuby J (2003) Immunology, 5th Edition, W.H. Freeman and Company, New York, New York, ISBN 0-7167-4947-5

• Immunology