Antigen Receptor Diversity

• Lymphocytes can mount a specific immune response against any foreign antigen because of the enormous diversity of their antigen receptors.
• Each lymphocyte has an antigen receptor of a single specificity, which is determined by genetic mechanisms during lymphocyte development in the bone marrow and thymus. These genetic mechanisms generate millions of different variants of the genes that encode the antigen receptors.
• Clonal selection theory: When B and T cells are activated in an antigen-specific manner, they divide and produce identical progeny. Only those lymphocytes that encounter their specific antigen are able to proliferate and differentiate into effector T or B cells. This explains why individuals have the capacity to develop antibodies to virtually any antigen, but only have antibodies that are specific to antigens to which they have been exposed.
• Clonal deletion: Developing lymphocytes with receptors specific for self-antigens are deleted at an early stage in lymphoid cell development. This allows B and T cells that are potentially self-reactive to be removed before they can mature, a process known as central tolerance.

Used with permission from Macmillan Publishers Ltd: Nature 421, 440-444, copyright 2003.