Central tolerance

From WikiMD's Wellness Encyclopedia

B cell central tolerance

Central tolerance is a critical process in the immune system that helps prevent the body from attacking itself, leading to autoimmunity. This mechanism operates primarily in the thymus for T cells and in the bone marrow for B cells, which are essential components of the adaptive immune system. Central tolerance is responsible for eliminating self-reactive lymphocytes during their development, ensuring that these cells do not initiate an immune response against the body's own tissues.

Mechanism[edit | edit source]

The process of central tolerance involves several key steps. In the thymus, immature T cells, known as thymocytes, undergo positive and negative selection. Positive selection ensures that T cells capable of recognizing self-major histocompatibility complex (MHC) molecules survive, while negative selection eliminates those T cells that have high affinity for self-antigens presented by MHC molecules. Similarly, in the bone marrow, developing B cells that react strongly to self-antigens are either edited to change their specificity or induced to undergo apoptosis, a process of programmed cell death.

T Cell Central Tolerance[edit | edit source]

During T cell development in the thymus, thymocytes expressing T cell receptors (TCRs) that fail to recognize self-MHC molecules are subjected to death by neglect, as they will not receive the necessary survival signals. Conversely, thymocytes that recognize self-MHC molecules with moderate affinity receive signals for survival and maturation, a process known as positive selection. Negative selection targets thymocytes that bind too strongly to self-antigens presented by MHC molecules, leading to their apoptosis. This process is facilitated by thymic epithelial cells and dendritic cells, which present self-antigens to developing T cells.

B Cell Central Tolerance[edit | edit source]

In the bone marrow, immature B cells that bind self-antigens with high affinity undergo receptor editing, an attempt to change their antigen specificity. If receptor editing fails to eliminate self-reactivity, the self-reactive B cells are eliminated through apoptosis. This ensures that emerging B cells are tolerant to self and reduces the risk of autoimmunity.

Importance[edit | edit source]

Central tolerance is crucial for preventing autoimmunity, a condition where the immune system mistakenly attacks the body's own cells and tissues. By eliminating self-reactive lymphocytes during their development, central tolerance helps maintain self-tolerance and immune homeostasis. However, central tolerance is not foolproof, and some self-reactive cells may escape into the peripheral circulation. Peripheral tolerance mechanisms exist to deal with these cells, including anergy, suppression by regulatory T cells, and deletion.

Clinical Significance[edit | edit source]

Defects in central tolerance can lead to the development of autoimmune diseases, such as Type 1 diabetes, multiple sclerosis, and systemic lupus erythematosus. Understanding the mechanisms of central tolerance is crucial for developing therapies aimed at restoring self-tolerance in autoimmune conditions. Additionally, manipulating central tolerance pathways has potential implications in transplantation and cancer immunotherapy, where enhancing or inhibiting immune responses can be beneficial.


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Contributors: Prab R. Tumpati, MD