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Basis of polyclonal response

Figure 2: Schematic diagram showing polyclonal response by B cells against linear epitopes. Note how each peptide can be recognized by two different clones, and how clones can recognize neighboring epitopes in an overlapping fashion. This is however a schematic representation involving linear epitopes. Recognition of conformational epitopes is more complex.

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

Clonality of B cells

Memory and naïve B cells normally exist in relatively small numbers. As the body needs to be able to respond to a large number of potential pathogens, it maintains a diverse repertoire of B cells. Consequently, while there is almost always at least one B (naive or memory) cell capable of responding to any given pathogen, there are very few exact duplicates. However, when a single B cell encounters an antigen to which it can bind, it can proliferate very rapidly, with the number of reactive cells doubling every 90 minutes. Each such group of cells with identical specificity towards the epitope is known as a clone, and is derived from a common "mother" cell. All of the "daughter" B cells match the original "mother" cell and secrete antibodies with identical paratopes.

Single antigen contains multiple overlapping epitopes

A single antigen can be broken down into multiple overlapping epitopes (see Figure 1). Many unique B cells may be able to bind to these different epitopes. This imparts even greater multiplicity to the overall response. All of these B cells can become activated and produce large colonies of plasma cell clones, each of which can secrete upto 2000 antibody molecules against each epitope per second.

Multiple clones recognize single epitope

In addition to different B cells reacting to different epitopes on the same antigen, B cells belonging to different clones may also be able to react to the same epitope. An epitope that can be attacked by many different B cells is said to be highly immunogenic. In these cases, the binding affinities for respective epitope-paratope pairs vary, with some B cell clones producing antibodies that bind strongly to the epitope, and others producing antibodies that bind weakly. This binding requires both the paratope and the epitope to undergo slight conformational changes in each others' presence.

Clonal selection

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: clones are selected for their fitness to attack the epitopes on the current pathogen.