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===V(D)J recombination=== {{Further|V%28D%29J recombination}} [[File:VDJ recombination.png|thumb|upright=1.25|Simplified overview of V(D)J recombination of immunoglobulin heavy chains]] Somatic recombination of immunoglobulins, also known as ''V(D)J recombination'', involves the generation of a unique immunoglobulin variable region. The variable region of each immunoglobulin heavy or light chain is encoded in several pieces—known as gene segments (subgenes). These segments are called variable (V), diversity (D) and joining (J) segments.<ref name = namazee/> V, D and J segments are found in [[immunoglobulin heavy chain|Ig heavy chains]], but only V and J segments are found in [[Immunoglobulin light chain|Ig light chains]]. Multiple copies of the V, D and J gene segments exist, and are tandemly arranged in the [[genome]]s of [[mammal]]s. In the bone marrow, each developing B cell will assemble an immunoglobulin variable region by randomly selecting and combining one V, one D and one J gene segment (or one V and one J segment in the light chain). As there are multiple copies of each type of gene segment, and different combinations of gene segments can be used to generate each immunoglobulin variable region, this process generates a huge number of antibodies, each with different [[wikt:paratope|paratopes]], and thus different antigen specificities.<ref name="Market">{{cite journal | vauthors = Market E, Papavasiliou FN | title = V(D)J recombination and the evolution of the adaptive immune system | journal = PLOS Biology | volume = 1 | issue = 1 | pages = E16 | date = October 2003 | pmid = 14551913 | pmc = 212695 | doi = 10.1371/journal.pbio.0000016 | doi-access = free }}</ref> The rearrangement of several subgenes (i.e. V2 family) for lambda light chain immunoglobulin is coupled with the activation of microRNA miR-650, which further influences biology of B-cells.{{cn|date=July 2024}} [[Recombination-activating gene|RAG]] proteins play an important role with V(D)J recombination in cutting DNA at a particular region.<ref name="Market"/> Without the presence of these proteins, V(D)J recombination would not occur.<ref name="Market"/> After a B cell produces a functional immunoglobulin gene during V(D)J recombination, it cannot express any other variable region (a process known as [[allelic exclusion]]) thus each B cell can produce antibodies containing only one kind of variable chain.<ref name=Janeway5/><ref>{{cite journal | vauthors = Bergman Y, Cedar H | title = A stepwise epigenetic process controls immunoglobulin allelic exclusion | journal = Nature Reviews. Immunology | volume = 4 | issue = 10 | pages = 753–61 | date = October 2004 | pmid = 15459667 | doi = 10.1038/nri1458 | s2cid = 8579156 }}</ref>
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