Where Does Somatic Hypermutation Occur?

Somatic hypermutation (SHM) occurs in

antigen-activated germinal center B cells

and contributes to antibody affinity maturation (1–8).

Where does somatic recombination occur?

Somatic recombination occurs physiologically in

the assembly of the B cell receptor and T-cell receptor genes (V(D)J recombination)

, as well as in the class switching of immunoglobulins. Somatic recombination is also important in the process of carcinogenesis.

Where do B cells undergo somatic hypermutation?

The germinal centers of peripheral lymphoid tissues

are the sites where somatic hypermutation, positive selection and differentiation of B cells with high-affinity receptors occur. Germinal centers are the only places in the body where antigen is retained for months or years in an extracellular location.

How does somatic hypermutation happen?

Somatic hypermutation involves

a programmed process of mutation affecting the variable regions of immunoglobulin genes

. Unlike germline mutation, SHM affects only an organism’s individual immune cells, and the mutations are not transmitted to the organism’s offspring.

Does somatic hypermutation occur in B and T cells?

AID is only expressed in activated B cells, and hence somatic hypermutation

only occurs after B cells have been activated by a helper T cell

.

What is the 12 23 rule?

The 12/23 rule, which is mediated at the level of RAG-1/2 recognition and cutting

^{4 , 5}

, specifies that

V(D)J recombination occurs only between a gene segment flanked by a 12-RSS and one flanked by a 23-RSS

¹

.

Why does somatic recombination occur?

Somatic recombination is

essential to protect genomes of somatic cells from DNA damage

but it also has important clinical implications, as it is a driving force of tumorigenesis leading to inactivation of tumor suppressor genes.

Do memory B cells undergo somatic hypermutation?

Once inside the germinal center, the B cells undergo

proliferation

, followed by mutation of the genetic coding region of their BCR, a process known as somatic hypermutation.

When does somatic hypermutation take place?

Cell Cycle Regulation of Somatic Hypermutation

AID is active during

the G1 phase of the cells cycle

(25, 145). Accordingly, G1 is also the cell cycle phase in which the highest levels of Us can be found in the immunoglobulin genes (25). Though, Us and abasic sites may persist into S phases.

What is the overall consequence for your immune system after it accomplishes somatic Hypermutations?

8) a) What is the overall consequence for your immune system after it accomplishes somatic hypermutations?

You produce antibodies with higher affinity (affinity maturation) due to random mutations in the variable regions

.

What is somatic DNA damage?

A somatic mutation is

change in the DNA sequence of a somatic cell of a

multicellular organism with dedicated reproductive cells; that is, any mutation that occurs in a cell other than a gamete, germ cell, or gametocyte.

How does affinity maturation occur?

Affinity maturation is the

process by which B cells increase their affinity for a particular antigen

. This “fine tuning” of B-cell specificity occurs through a repeated process of somatic hypermutation of B-cell receptors and subsequent clonal selection.

How many V genes do humans have?

In humans, there are approximately

50 known functional V

(variable) segments [3-6], 27 known functional D (diversity) segments [3,7,8], and six known functional J (joining) segments [3,8,9] available within a single locus for assembly into heavy chain genes.

Do T cells pass somatic hypermutation?

Somatic hypermutation does not occur in T-cell receptor genes

, so that variability of the CDR1 and CDR2 regions is limited to that of the germline V gene segments. All the diversity in T-cell receptors is generated during rearrangement and is consequently focused on the CDR3 regions.

What enzyme drives the process of somatic recombination in B cells?

Both somatic hypermutation and switch recombination are carried out by a B cell specific enzyme:

Activation-Induced cytidine Deaminase (AID)

. This protein modifies the chemical nature of DNA, converting cytidines into another base called uracil, a process known as cytidine deamination.

Where are germinal centers located?

Germinal centers or germinal centres (GCs) are

transiently formed structures within B cell zone (follicles) in secondary lymphoid organs – lymph nodes, ileal Peyer’s patches, and the spleen

– where mature B cells are activated, proliferate, differentiate, and mutate their antibody genes (through somatic hypermutation …