selfreactivity

Selfreactivity refers to the property of immune receptors, such as B cell receptors (BCRs) or T cell receptors (TCRs), or antibodies, to recognize and bind self-antigens. In a healthy immune system, some level of selfreactivity exists as part of broad pathogen recognition, but highly self-reactive clones are typically controlled or eliminated to prevent damage to the body.

In development and maintenance, selfreactivity is shaped by tolerance mechanisms. Central tolerance occurs during lymphocyte development in primary organs: B cells in the bone marrow and T cells in the thymus undergo negative selection, receptor editing, or clonal deletion to reduce self-reactivity. Peripheral tolerance includes mechanisms such as anergy, regulatory T cell suppression, and clonal ignorance, which prevent self-reactive cells from causing autoimmunity even if they escape central tolerance. Somatic hypermutation and affinity maturation can alter selfreactivity in mature B cells, sometimes increasing autoreactivity or, alternatively, being countered by tolerance checkpoints.

Clinical relevance centers on autoimmunity. When selfreactivity is inadequately regulated, autoreactive B and T cells can attack self tissues, contributing to diseases such as systemic lupus erythematosus, type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. Some autoreactive antibodies are also present in healthy individuals as natural autoantibodies, typically with broad reactivity but limited pathogenic potential. Research in selfreactivity aims to understand tolerance breakdown, identify autoreactive clones, and develop therapies that selectively suppress harmful self-reactive responses while preserving protective immunity.

Note: the term selfreactivity can appear in other disciplines, such as chemistry, to describe molecules that react with themselves. This article concentrates on immunological selfreactivity.