The immune system protects the body from foreign invaders like bacteria and viruses. To do this effectively, it must distinguish between threats and the body’s own healthy components. Negative selection is a quality control process for developing immune cells, ensuring they do not attack the body’s own tissues. This mechanism helps the immune system tolerate self-components while fighting external dangers.
Shaping T Cells for Self-Tolerance
T cells, a type of white blood cell, mature primarily within the thymus. During this maturation, immature T cells encounter self-proteins, also known as self-antigens, presented by Major Histocompatibility Complex (MHC) molecules on thymic cells. This interaction determines the T cell’s fate.
T cells possess T cell receptors (TCRs) that recognize specific antigen-MHC combinations. If a developing T cell’s TCR binds too strongly to a self-antigen, it receives a signal triggering programmed cell death, called apoptosis. This eliminates highly self-reactive T cells, preventing them from attacking the body’s own tissues. Only T cells tolerant to self-antigens and capable of recognizing foreign invaders survive.
Refining B Cells for Self-Tolerance
B cells, another type of lymphocyte, mature primarily within the bone marrow. Here, they also undergo a selection process to prevent self-reactivity. Similar to T cells, newly formed B cells are tested for their interaction with self-antigens. If an immature B cell strongly binds to self-antigens, it faces elimination to prevent the production of antibodies that could target the body’s own components.
B cells have a unique mechanism called “receptor editing” to address self-reactivity. Instead of immediate deletion, self-reactive B cells can modify their antibody genes to create a new receptor with a different specificity. This allows the B cell to “edit” its antigen receptor, potentially salvaging it from programmed cell death. If receptor editing fails to produce a non-self-reactive receptor, the B cell is eliminated through apoptosis. This ensures only B cells capable of producing antibodies against foreign threats are released into the bloodstream.
When Immune Control Goes Wrong
When negative selection is impaired or incomplete, self-reactive T or B cells can escape into circulation. These immune cells can then become activated and mistakenly target healthy tissues, leading to an immune response against the body itself. This misdirected attack is the underlying cause of autoimmune diseases.
Conditions like Type 1 Diabetes, Rheumatoid Arthritis, and Lupus exemplify the consequences of compromised negative selection. In Type 1 Diabetes, the immune system attacks insulin-producing cells in the pancreas. Rheumatoid Arthritis involves the immune system attacking the lining of joints, causing inflammation and damage. Lupus can affect various organs and tissues, leading to widespread inflammation and damage. Proper negative selection is essential for maintaining health and preventing these conditions.