<unk><unk>  occurs after activation of a mature B cell via its membrane-bound antibody molecule (or B cell receptor) to generate the different<unk> es of antibody, all with the same variable domains as the original antibody generated in the immature B cell during the process of V(D)J recombination, but possessing distinct constant domains in their heavy chains. Naïve mature B cells produce both IgM and IgD, which are the first two heavy chain segments in the<unk>  locus. After activation by antigen, these B cells proliferate. If these activated B cells encounter specific signaling molecules via their CD40 and cytokine receptors (both modulated by T helper cells), they undergo antibody<unk><unk>  to produce IgG, IgA or IgE antibodies. During<unk><unk> , the constant region of the<unk>  heavy chain changes but the variable regions do not, and therefore antigenic specificity, remains the same. This allows different daughter cells from the same activated B cell to produce antibodies of different isotypes or subtypes (e.g. IgG1, IgG2 etc.). In humans, the order of the heavy chain exons is as follows: # μ - IgM # δ - IgD # γ3 - IgG3 # γ1 - IgG1 # α1 - IgA1 # γ2 - IgG2 # γ4 - IgG4 # ε - IgE # α2 - IgA2<unk><unk>  occurs by a mechanism called<unk>  switch recombination (CSR) binding.<unk>  switch recombination is a biological mechanism that allows the<unk>  of antibody produced by an activated B cell to change during a process known as isotype or<unk><unk> . During CSR, portions of the antibody heavy chain locus are removed from the chromosome, and the gene segments surrounding the deleted portion are rejoined to retain a functional antibody gene that produces antibody of a different isotype. Double-stranded breaks are generated in DNA at conserved nucleotide motifs, called switch (S) regions, which are upstream from gene segments that encode the constant regions of antibody heavy chains; these occur adjacent to all heavy chain constant region genes with the exception of the δ-chain. DNA is nicked and broken at two selected S-regions by the activity of a series of enzymes, including activation-induced (cytidine) deaminase (AID), uracil DNA glycosylase and apyrimidic/apurinic (AP)-endonucleases. The intervening DNA between the S-regions is subsequently deleted from the chromosome, removing unwanted μ or δ heavy chain constant region exons and allowing substitution of a γ, α or ε constant region gene segment. The free ends of the DNA are rejoined by a process called non-homologous end joining (NHEJ) to link the variable domain exon to the desired downstream constant domain exon of the antibody heavy chain. In the absence of non-homologous end joining, free ends of DNA may be rejoined by an alternative pathway biased toward microhomology joins. With the exception of the μ and δ genes, only one antibody<unk>  is expressed by a B cell at any point in time. While<unk>  switch recombination is mostly a deletional process, rearranging a chromosome in "cis", it can also occur (in 10 to 20% of cases, depending upon the Ig<unk>  as an inter-chromosomal translocation mixing<unk>  heavy chain genes from both alleles.
Immunoglobulin class switching
Alloantigen recognition
Antibody opsonization
Memory T cell inflation
Fragment antigen-binding
Complement-dependent cytotoxicity
Immune tolerance
Antibody-dependent enhancement