Somatic hypermutation and affinity maturation

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Somatic hypermutation and affinity maturation


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Somatic hypermutation and affinity maturation

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USMLE® Step 1 style questions USMLE

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An activated B cell located in the spleen binds an antigen and is activated via cytokines from a nearby T cell. An enzyme is then expressed in the B cell, which causes random nucleotides to be changed in the B cell receptor variable region. Subsequent generations of daughter cells of this B cell develop progressively stronger binding to this antigen. Which of the following correctly describes this process?  

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Somatic hypermutation p. 99

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Content Reviewers

The immune response is highly specific for each invader, and that’s because the cells of the adaptive immune response have unique receptors that can differentiate friendly bacteria from deadly pathogens by their unique parts - called antigens.

The key cells of the adaptive immune response are the lymphocytes - the B and T cells which have unique antigen receptors known as the B cell receptor or BCR and T cell receptor or TCR respectively.

Both B cells and T cells undergo a process called VDJ rearrangement to generate a massively diverse set of receptors.

B cells can further enhance the diversity of their BCR repertoire using a process called somatic hypermutation, and the result is that the cells that emerge will have a stronger and more specific response to the antigen - and this is called affinity maturation.

Now remember, that the B cell receptor is essentially an antibody except that it’s attached to the surface of the B cell.

And each B cell receptor or antibody has two general parts- the variable region which binds antigen and the constant region which determines the specific antibody class - IgM, IgG, IgA, IgD, or IgE.

When B cell receptors are initially created it’s done in the absence of antigen.

Somatic hypermutation only happens in activated B cells, and not in T cells.

This happens at sites where B cells are activated and T cells are also present- basically in germinal centers within lymph nodes and the spleen.


Somatic hypermutation and affinity maturation are two mechanisms by which the immune system can adapt to better recognize and neutralize pathogens. Somatic hypermutation is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it (e.g. microbes), whereas affinity maturation refers to the process of increasing the specificity and strength of the interaction between an antibody and its target antigen to increase the effectiveness of the immune response.


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