Page last updated: 2024-10-24

positive regulation of isotype switching

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of isotype switching. [GOC:go_curators]

Positive regulation of isotype switching is a complex biological process that involves a series of tightly regulated steps leading to the production of different antibody classes (isotypes) from the same antibody gene. Here's a detailed breakdown:

**1. Activation of B cells:** The process begins with the activation of B lymphocytes (B cells) by an antigen. This activation triggers the expression of activation-induced cytidine deaminase (AID), a key enzyme for isotype switching.

**2. DNA recombination:** AID introduces DNA lesions, primarily deaminations of cytosine bases, in the switch regions (S regions) located upstream of each antibody constant region gene. These deaminations lead to the formation of uracil bases.

**3. DNA repair:** Uracil bases are recognized by DNA repair enzymes, which initiate a complex process involving double-strand breaks, DNA resection, and homologous recombination. This process leads to the deletion of intervening DNA segments between the S regions, bringing a new constant region gene in close proximity to the variable region gene.

**4. Expression of new isotype:** Once the DNA rearrangement is complete, the B cell expresses a new isotype of antibody, determined by the newly recombined constant region gene. This switch in isotype allows the B cell to produce antibodies with different effector functions, such as complement activation, antibody-dependent cellular cytotoxicity (ADCC), or binding to specific receptors on immune cells.

**5. Regulation:** Several factors regulate isotype switching, including cytokines, transcription factors, and the specific antigen encountered by the B cell. For instance, the cytokine interleukin-4 (IL-4) promotes switching to IgE, while IFN-gamma promotes switching to IgG2a.

**6. Importance:** Isotype switching is essential for the adaptive immune response, allowing B cells to generate antibodies with diverse effector functions, which are crucial for mounting effective immune responses against various pathogens.'
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Proteins (3)

ProteinDefinitionTaxonomy
Histone-lysine N-methyltransferase KMT5CA histone-lysine N-methyltransferase KMT5C that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q86Y97]Homo sapiens (human)
Histone-lysine N-methyltransferase KMT5BA histone-lysine N-methyltransferase KMT5B that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q4FZB7]Homo sapiens (human)
TP53-binding protein 1A TP53-binding protein 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q12888]Homo sapiens (human)

Compounds (4)

CompoundDefinitionClassesRoles
s-adenosylhomocysteineS-adenosyl-L-homocysteine : An organic sulfide that is the S-adenosyl derivative of L-homocysteine.

S-Adenosylhomocysteine: 5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions.
adenosines;
amino acid zwitterion;
homocysteine derivative;
homocysteines;
organic sulfide
cofactor;
EC 2.1.1.72 [site-specific DNA-methyltransferase (adenine-specific)] inhibitor;
EC 2.1.1.79 (cyclopropane-fatty-acyl-phospholipid synthase) inhibitor;
epitope;
fundamental metabolite
(5-bromo-3-pyridinyl)-[4-(1-pyrrolidinyl)-1-piperidinyl]methanonearomatic carboxylic acid;
pyridinemonocarboxylic acid
entecavirbenzamides;
N-acylpiperidine
6,7-dimethoxy-2-(pyrrolidin-1-yl)-n-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine: a SETD8 inhibitor; structure in first source