Affinity Maturation: Study with Video Lessons, Practice Problems & Examples

Affinity maturation is a crucial process in the immune system that enhances the effectiveness of antibodies during an infection. It involves B cells accumulating mutations in their B cell receptors (BCRs), particularly in the variable region that determines antigen binding. B cells with mutations that improve binding proliferate, while those with less effective mutations do not. This natural selection leads to a population of B cells capable of producing highly effective antibodies, improving the body's defense against specific antigens over time. Together with antibody class switching, affinity maturation ensures a robust immune response.

Affinity Maturation

In this video, we're going to begin our lesson on a process called affinity maturation. And so here we're asking you guys a question that says, how does our immune system ensure mass production of the most effective antibody during an infection? And so one of the answers to this question is through the process called antibody class switching, which recall we talked about before in some of our previous lesson videos, and allows B cells and plasma cells to ultimately switch the class of antibody that they will produce and create a more effective antibody class. However, another answer to this question is the process of affinity maturation, which is going to allow B cells and plasma cells to continuously create more and more effective antibodies over time. And so what's important to note is that as B cells proliferate and divide, it's more likely that mutations will occur. And these mutations can occur in the variable region of the BCR or antibody genes, and recall that the variable region is the region that is going to control the antigen binding site. And so this can cause changes in the antigen binding site and the ability for the BCR or antibody to bind its antigen. And so, ultimately, these mutations that occur in the variable region of the BCR or antibody genes and the changes that occur in the BCR or antibodies' ability to bind its antigen can lead to a process that we refer to as affinity maturation. And so affinity maturation can be defined as a form of natural selection among B cells allowing for mass production of more effective antibodies over time. And so the way that this process works is that B cells that accumulate mutations in their BCRs that allow them to bind their antigen more effectively are actually going to be a lot more likely to proliferate and divide and create an army of identical clones that can bind more effectively. However, the B cells that end up accumulating mutations in their BCRs that allow them to bind less effectively to their antigen are going to be less likely to proliferate and divide, and so they will not be able to divide. And so over time, as this continues to happen during an infection, the majority of B cells during an infection are going to be able to bind the antigen more and more effectively as time proceeds. And so if we take a look at our image down below, we can get a better understanding of this process of affinity maturation. Select naturally selecting for B cells that bind more and more effectively. And so what you'll notice is that in this image we have a B cell here that has these B cell receptors or BCRs. And notice that within these B cells, there are some green pluses throughout and there are some red pluses throughout as well. And so it's important to note that the green pluses represent more effective B cells, and those more effective B cells are going to be more likely to proliferate and divide. And then the red pluses actually represent less effective B cells that bind the antigen not as well. And so those are less likely to proliferate. They do not proliferate. And, of course, the more green pluses there are, the more capable the BCR and antibody are capable of binding to its antigen. And the same thing goes with the more red pluses, the less capable it is at binding. And so notice that at the very top what we have is a B cell that is pretty capable of binding to its antigen. And so this B cell that's capable of binding to its antigen is going to be promoted to proliferate and divide. And so notice that as this B cell divides, mutations can accumulate in the variable region of its BCR and antibody genes. And so that's going to change the ability for those BCRs and antibodies to bind their antigen. And so notice that sometimes the mutations lead to a decreased ability to bind to the antigen. And if that's the case, these mutations, these B cells that accumulate mutations that lead to less effective binding, they are not likely to proliferate, and so notice they stop dividing here. However, sometimes the mutations will lead to improved ability to bind the antigen, and so notice here we have 2 green pluses representing mutations that occurred that lead to improved binding. And so this one here is more likely to proliferate and divide, and so when it proliferates and divides, again, mutations are likely to occur. And if the mutations lead to decreased binding ability of the BCR or antibody to the antigen, again, these cells will not be likely to divide and proliferate, so they stop dividing. However, if these mutations lead to yet even better, more effective B cells, notice there are 3 green pluses here, then this one here is going to be more likely to proliferate. And so, ultimately, what you see here is that this one here can proliferate even more, again accumulating more and more improved binding ability over time. And then as these divide, again, you start to get an army of effective B cells that are more and more effective as time proceeds as they divide and accumulate mutations that allow them to bind better and better over time. And so ultimately what we're saying here is that between the process of antibody class switching that we talked about in our previous lesson videos and the process of affinity maturation here that we're discussing in this video, over time, B cells and plasma cells are going to be able to produce more and more effective BCRs and antibodies over time. And so what this means is that our bodies are going to get better and better at defending themselves from specific types of antigens over time. And so this concludes our brief lesson on affinity maturation, and we'll be able to get some practice applying these concepts as we move forward in our course. And so I'll see you all in our next video.

True or False? The process of affinity maturation generates antibodies with an increasing capacity to bind antigens and thus to more efficiently bind to, neutralize, and eliminate microbes.

• A. True.
• B. False.

How does an antibody’s ability to bind an antigen increase as B cells multiply?

• A. Genetic rearrangement of the DNA encoding the antibody’s constant region occurs with each B cell generation.
• B. Genetic mutations of the DNA encoding the antibody’s variable region occur with each B cell generation.
• C. Variation in the amino acid sequence of the antibody stem occurs & allows the antibody to bind various antigens.
• D. Genetic mutations of the DNA encoding the antibody occur changing the antibody into a BCR.

Which of the following statements about antibody affinity maturation is true?

• A. It is a form of natural selection ensuring only antibodies that most effectively bind the antigen are produced.
• B. It occurs when mutations happen in the DNA encoding the variable region of the antibody.
• C. It ensures that only B cells with BCRs that effectively bind the antigen are allowed to proliferate.
• D. After an affinity maturation cycle, the majority of the B cell population will create antibodies that bind the antigen.
• E. A and B.
• F. B and C.
• G. All of the above are true about affinity maturation.

Here’s what students ask on this topic:

What is affinity maturation in the immune system?

Affinity maturation is a process in the immune system that enhances the effectiveness of antibodies during an infection. It involves B cells accumulating mutations in their B cell receptors (BCRs), particularly in the variable region that determines antigen binding. B cells with mutations that improve binding proliferate, while those with less effective mutations do not. This natural selection leads to a population of B cells capable of producing highly effective antibodies, improving the body's defense against specific antigens over time. Together with antibody class switching, affinity maturation ensures a robust immune response.

How does affinity maturation improve antibody effectiveness?

Affinity maturation improves antibody effectiveness by promoting the proliferation of B cells with mutations in their B cell receptors (BCRs) that enhance antigen binding. As B cells divide, mutations occur in the variable region of the BCRs. B cells with mutations that result in better antigen binding are more likely to proliferate, while those with less effective mutations do not. Over time, this natural selection process leads to a population of B cells that produce highly effective antibodies, thereby enhancing the immune response against specific antigens.

What role do mutations play in affinity maturation?

Mutations play a crucial role in affinity maturation by introducing changes in the variable region of B cell receptors (BCRs). These mutations can either improve or reduce the ability of BCRs to bind to antigens. B cells with mutations that enhance antigen binding are more likely to proliferate and create an army of identical clones, while those with less effective mutations do not proliferate. This natural selection process ensures that over time, the majority of B cells produce highly effective antibodies, thereby improving the immune response.

How does affinity maturation differ from antibody class switching?

Affinity maturation and antibody class switching are both processes that enhance the immune response, but they operate differently. Affinity maturation involves the accumulation of mutations in the variable region of B cell receptors (BCRs), leading to the selection of B cells that bind antigens more effectively. In contrast, antibody class switching changes the class of antibody produced by B cells (e.g., from IgM to IgG) without altering the antigen specificity. While affinity maturation improves the binding affinity of antibodies, class switching allows the immune system to use different antibody classes to better combat various types of infections.

Why is the variable region of B cell receptors important in affinity maturation?

The variable region of B cell receptors (BCRs) is crucial in affinity maturation because it determines the antigen binding site. Mutations in this region can alter the binding affinity of the BCRs to their specific antigens. During affinity maturation, B cells with mutations that improve binding to the antigen are more likely to proliferate, while those with less effective mutations do not. This natural selection process ensures that over time, the population of B cells produces highly effective antibodies, enhancing the immune response against specific antigens.