Organization and expression of immunoglobulin genes

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Antibodies are Y‑shaped proteins that help the immune system recognize and neutralize microbes. Each antibody has two heavy chains and two light chains, held together by disulfide bonds.

The parts that make up these chains come from sets of genes on different chromosomes. For the heavy chain, the variable region is built from V, D, and J segments joined together, followed by a constant region (C). For the light chain, the variable region comes from V and J segments joined together, followed by a constant region. Light chains can be either kappa (κ) or lambda (λ).

During B cell development in the bone marrow, these gene segments are rearranged in a process called V(D)J recombination. This creates a unique variable region for each antibody. The rearrangement is guided by recombination signal sequences and enzymes called RAG‑1 and RAG‑2, using a 12/23 base pair rule to ensure correct joining.

The heavy-chain gene rearranges first in the early stages, producing a μ heavy chain that pairs with a surrogate light chain to form a pre‑B cell. Light‑chain genes then rearrange, and an immature B cell with membrane‑bound IgM emerges.

As B cells mature, they mostly display membrane IgM and IgD on their surface. When a B cell meets an antigen, it can switch to producing other antibody classes (isotypes) such as IgG, IgA, or IgE. Isotype switching changes the constant region of the heavy chain (not the variable region) by looping out and reconnecting DNA between switch regions. Signals from other immune cells and cytokines (for example, interleukin‑4) guide this switching.

During an immune response, B cells divide and accumulate mutations in the antibody variable regions, a process called somatic hypermutation. These mutations can increase how tightly an antibody binds its target.

Activated B cells can become plasma cells that secrete large amounts of antibody, or memory B cells that respond more quickly if the same antigen appears again.

In short, antibody diversity comes from rearranging different V, D, J, and C gene segments during B‑cell development, followed by RNA processing, class switching, and somatic mutation as the immune response unfolds.