Immunoglobulin Genes and Generation of Diversity
المؤلف:
Stefan Riedel, Jeffery A. Hobden, Steve Miller, Stephen A. Morse, Timothy A. Mietzner, Barbara Detrick, Thomas G. Mitchell, Judy A. Sakanari, Peter Hotez, Rojelio Mejia
المصدر:
Jawetz, Melnick, & Adelberg’s Medical Microbiology
الجزء والصفحة:
28e , p138
2025-07-19
503
The ability of an individual to produce an extremely large number of immunoglobulin molecules (~3 × 1011) with a relatively small number of genes has evolved through special genetic mechanisms. This occurs because the immunoglobulin genes undergo somatic recombination, which generates an enormous diversity of antibody specificities.
Each immunoglobulin chain consists of a variable (V) and a constant (C) region. For each type of immunoglobulin chain, that is, kappa light chain (κ), lambda light chain (λ), and the five heavy chains (γH, μH, αH, δH, and εH), there is a separate pool of gene segments located on different chromosomes. In humans the multigene families are found on the following chromosomes: λ, chromosome 22; κ, chromosome 2; and the heavy chain family, chromosome 14. Each of the three gene loci contains a set of different V gene segments that are separated from the C gene segments. During B-cell differentiation, the DNA is rearranged to bring the identified gene segments adjacent to each other in the genome.
In summary, the gene rearrangement process is complex and involves a number of steps. The variable region of each L chain is encoded by two gene segments: V and J. The variable region of each H chain is encoded by three gene segments: V, D, and J. The segments are united into one functional V-variable gene by DNA rearrangement. Each assembled V-variable gene is then transcribed with the appropriate C-constant gene to produce a messenger RNA (mRNA) that encodes for the complete peptide chain. L and H chains are synthesized separately on polysomes and then assembled in the cytoplasm to form H2 L2 chain units. The carbohydrate portion of the Ig molecule is then added during passage through the membrane components of the cell (eg, Golgi apparatus), and the immunoglobulin molecule is released from the cell.
T his gene rearrangement mechanism generates an enormous variety of immunoglobulin molecules. Antibody diversity depends on (1) multiple V, D, and J gene segments; (2) combinatorial association, that is, the association of any V gene segment with any D or J segment; (3) the random combining of different L and H chains; (4) somatic hyper mutation; and (5) junctional diversity produced by imprecise joining during rearrangement.
الاكثر قراءة في المناعة
اخر الاخبار
اخبار العتبة العباسية المقدسة
