somatic diversification of immunoglobulins

Definition

Target type: biologicalprocess

The somatic process that results in the generation of sequence diversity of immunoglobulins. [GOC:add, GOC:ma, ISBN:0781735149]

Somatic diversification of immunoglobulins is a remarkable process that generates an extraordinarily diverse repertoire of antibodies, enabling the immune system to recognize and neutralize a vast array of pathogens. It occurs primarily in B lymphocytes, the cells responsible for humoral immunity. This process involves a series of genetic rearrangements, mutations, and selection events that shape the antibody variable regions, the portions responsible for antigen binding.

The initial diversity stems from the rearrangement of gene segments during B cell development. The immunoglobulin gene locus is organized into three distinct segments: variable (V), diversity (D), and joining (J) segments. Each segment exists in multiple copies, and their random combination leads to a vast array of possible VDJ recombinations. This combinatorial diversity is further augmented by the addition of nucleotides at the junctions between the segments, known as N-nucleotide addition, catalyzed by the terminal deoxynucleotidyl transferase (TdT) enzyme.

Once a B cell has rearranged its immunoglobulin genes, it expresses a unique antibody on its surface. These immature B cells undergo a process called affinity maturation in the germinal centers of lymph nodes. This process involves interactions with antigen-presenting cells and helper T cells, which trigger further genetic modifications within the rearranged V regions.

The primary mechanism for affinity maturation is somatic hypermutation, a process that introduces mutations in the variable region at a high rate. This high mutation rate is achieved by the activation-induced cytidine deaminase (AID) enzyme, which deaminates cytosine bases to uracil. These mutations are then processed by DNA repair mechanisms, leading to nucleotide substitutions, insertions, or deletions within the V region.

The resulting antibody variants are then displayed on the surface of B cells and undergo selection based on their binding affinity for the antigen. B cells with higher affinity antibodies are preferentially selected for survival and further differentiation, while those with lower affinity are eliminated. This process of clonal selection ensures that the immune system produces antibodies with progressively higher affinity for the specific antigen.

The somatic diversification of immunoglobulins is a highly regulated and complex process that relies on a combination of genetic rearrangements, mutations, and selection events. This intricate interplay allows the immune system to generate a diverse and adaptable antibody repertoire, capable of recognizing and neutralizing a vast array of pathogens, ultimately contributing to the protection of the host from infectious diseases.'
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Proteins (1)

Compounds (33)