Clonal deletion

Clonal deletion is the removal through apoptosis of B cells and T cells that have expressed receptors for self before developing into fully immunocompetent lymphocytes. This prevents recognition and destruction of self host cells, making it a type of negative selection or central tolerance. Central tolerance prevents B and T lymphocytes from reacting to self. Thus, clonal deletion can help protect individuals against autoimmunity. Clonal deletion is thought to be the most common type of negative selection. It is one method of immune tolerance.

Frank Macfarlane Burnet proposed autoreactive cells would be terminated before maturation in order to prevent further proliferation in his study in 1959. There are millions of B and T cells created in the bone marrow and thymus, respectively. Each of these lymphocytes express specificity to a particular epitope, or the part of an antigen to which B cell and T cell receptors recognize and bind. There is a large diversity of epitopes recognized and, as a result, it is possible for some B and T lymphocytes to develop with the ability to recognize self. B and T cells are presented with self antigen after developing receptors while they are still in the primary lymphoid organs. Those cells that demonstrate a high affinity for this self antigen are often subsequently deleted so they cannot create progeny, which helps protect the host against autoimmunity. Thus, the host develops a tolerance for this antigen, or a self tolerance.

B and T lymphocytes are tested for their affinity for self /peptide complexes before leaving the primary lymphoid organs and entering into the periphery. If they demonstrate high affinity for self-antigen, one method of preventing autoimmunity is through clonal deletion. This is where the lymphocyte would receive apoptotic signals from antigen-presenting cell (APCs). It is important to note that not all lymphocytes expressing high affinity for self-antigen undergo clonal deletion. B lymphocytes can also participate in light chain receptor editing, V_H gene replacement, or be released and later undergo negative selection in the periphery. T lymphocytes can instead undergo clonal arrest, clonal anergy, and clonal editing. If autoreactive cells escape clonal deletion in either the thymus or the bone marrow, there are mechanisms in the periphery involving T regulatory cells to prevent the host from obtaining an autoimmune disease. However, for both B and T cells in the primary lymphoid organs, clonal deletion is the most common form of negative selection.

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