immunoglobulin class expression

[charmaine]

Hey guys,

was wondering if any one could give me or point me towards a simple explanation of the class switching in antibodies.

 

It seems that everything I look at on the web doesn't really explain it or how it happens.

 

thankyou!

[kixxer]

Hey guys' date='

was wondering if any one could give me or point me towards a simple explanation of the class switching in antibodies.

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Ok, I´ll give my best:)

 

So basically, there are many "steps" of the antibody immune response against pathogens. At first after infection, the plasma cells produce IgM antibodies, which posess a pentamer structure, high avidity and low affinity.Once the IgM response has been initiated, the plasma cells undergo a process called class switch, which results in the production of IgG or other antibody isotypes.

 

The "genes" for antibodies consist of a high number of boxes, called the V (variable), D (diversity), J (Joining) and C (constant) regions. There are multiple types of each of these boxes, located behind each other. Heres a picture to get the idea:

 

 

Well, in the maturation process the B cell undergoes a series of somatic recombinations, in which the V, D and J gene boxes are "glued" together to make up a new gene (as named in the picture). This New gene represents the whole variable region of the antibody, the region which actually recognizes non-self material (pathogens etc.). The reason why the Variable region of the antibody is produced from different gene-fragments (V,D and J boxes) is to ensure that B cells have an almost unlimited amount of different variable regions and in this way are able to recognize all non-self material that gets into the body. This variability is even further induced by unprecise recombination of the V,D,J-boxes, thus allowing even more different variable regions for the antibodies.

 

Hope you are following me... (IT´s hard for a non-english person to write this stuff...)

 

So, this newly combined Variable region (consisting of different V,D and J boxes) is always combined with one more gene-box, the C (constant) region. There are many different constant regions, and all different antibody subtypes differ in their constant region (They must have the same reactivity against pathogens, so they all posess the same VDJ-region). Here is a good picture:

 

 

In the beginning of the immune response, the first C-box which follows the newly recombined VDJ-segments is the C-IgM box. This is why IgM is produced in the beginning. With time, the immune system needs to replace the IgM against other subtypes of antibodies, which work more efficiently. So here IgG is the main candidate, offering low avidity, very high affinity, higher stabilty, transplacental transport etc..

The class switch is induced by many factors, such as cytokines, CD40/CD40L stimulation pathways, which give the Plasma cell the signal it needs to change the type of antibody it produces.

 

So once the cell gets these signals, the e.g. C-IgG box you see on the picture will be recombined to the VDJ-Region (and in the next step the IgA box). This process deletes all other C-regions upstream of the C-IgG, which makes it unpossible for a plasma cell to produce IgM after it has been switched to other isotypes, because the C-IgM-region is permanently deleted from the DNA. So all that chagnes is the C-region (according to the isotype you want), the VDJ-region stays the same.

 

uuhh...this is complicated, I hope I didn´t make any mistakes (expert help?).

 

greets,

kix

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[charmaine]

Thankyou kixxer!