The B-Cell Population Produces Antibodies to Millions of Different AntigensfYet the Antibody-Antigen Interaction Is Specific
Antibodies bind to antigen through their antigen-binding sites. Each antigen-binding site is formed by the steric interaction of the V∣ and V∣∣ domains, which come in close contact because of the three-dimensional folding of the glycoprotein chains on which they reside.
This steric interaction essentially forms a cleft, and any antigenic structure that fits into this cleft is recognized and binds to the antigen-binding site. Therefore, if an antigen can bind to the antigen-combining site on the BCR, the B cell is eventually (after a complex set of signal interactions) triggered to replicate (clonally expand), giving rise to many uidenticaΓ,B cells, which eventually produce and secrete the soluble immunoglobulin specific for that antigen.It is important to stress that antibody-antigen responses are specific. Antibodies produced after exposure to an antigen will only bind to that antigen or to other antigens structurally similar to the original antigen (cross-reaction). The question is, mHow does the immune system manage to respond to literally several million different foreign antigens in a specific way?” Three facts are crucial to understand this situation. First, the BCR is an immunoglobulin, and the specificity of the immunoglobulin secreted by a particular B cell is the same as the specificity of its BCR. Second, an individual B cell can only have BCRs of identical specificity. Third, essentially each B cell (and there are millions) in the body has a BCR with a different antigen-combining site, because B cells undergo random genetic mutations in the genes coding for their Vl and Vh domains during their early development (ontogeny). Because these domains make up the antigen-combining site, a single amino acid change in either of the regions changes the steric interaction of these domains, giving rise to different “clefts” with different antigen-combining abilities.