Use of Computer Models and Animations to Teach about B Cell (antibody) and T Cell Recombination (TCR).

INTRODUCTION

This manuscript presents a technique on how to use both computer models and animations to teach about the process of recombination in B cells. This is a traditionally difficult topic taught in both microbiology and immunology classes. It is frequently difficult for students to understand the process of alternative splicing and how it is used to create a vast array of different antibody molecules. At the most basic level, the students are taught that antibodies have heavy and light chains and constant and variable regions and that the host cell can make many different types of antibodies by combining these regions. At the more advanced level, the students are taught that the heavy chain is formed by randomly joining together different V, D, J, and C regions. The light chain is formed by randomly selecting various V, J, and C regions.

Active learning techniques are presented to help teach the students about this process. In introductory classes, the instructor can teach the students how antibody molecules are made. In more advanced classes, this topic can be expanded, and the students can also learn how T cell receptors are made. Initially, the students are shown an animation of antibody recombination where they can select to see the different randomly generated segments coming together. Then, they look at their computers to see the different segments of antibodies shown in different colors, and they can select one fragment from the different sections. We feel that the use of these different techniques is important in reinforcing the topic.

This series of activities will enable students to learn about various topics relating to recombination in both T and B cells. To ensure that all students have the requisite basic and specific knowledge on this subject, the instructor should first conduct a discussion with the class. Depending on the outcome of this discussion, the instructor may have to lecture to the class or direct students to read sections in their textbook.

PROCEDURE

The instructor should begin by asking the students what makes up the general structure of an antibody. Many students should be able to remember that there are heavy and light chains and constant and variable regions. Some might also know that there are kappa and lambda light chains. If not, the instructor should direct the students to their textbook. There should then be a discussion of the regions found in the heavy chains and light chains of antibody molecules. The instructor should make sure that everyone understands that the heavy chain contains V, D, J, and C regions while the light chain contains only V, J, and C regions.

Next, the instructor should ask the students about splicing and alternate splicing. The students should remember that one of the post-transcriptional modifications of an RNA molecule is that splicing occurs. It should then be explained that, in making antibody molecules, alternative splicing occurs, which means that there is a choice of which segments are chosen. Also, some of the splicing steps occur at the DNA level and some at the RNA level. By discussing the different choices that a cell can make, it will become clear how combinational diversity plays a role in making antibody molecules. For more advanced classes, there should also be a discussion of the αβ and γδ T cell receptors and the different regions which comprise them. The notion that the process of forming these receptors is similar to making antibody molecules should be discussed.

Animation

The concepts in the discussion should be reinforced by showing the students an animation of the formation of both the heavy and light chains in an antibody. Some students might want to use their own computers to watch the animation more easily. Students and faculty may decide to look at each chain separately and learn about the different parts of each chain. They could then look at the entire process of both the heavy and light chains being formed and then joining together. The animation teaches the students about how antibody molecules can become very diverse due to the number of different segments and also due to the fact that there are both kappa and lambda light segments. Appendix 1 contains a picture of this animation and a link to the program.

Computer models

To use more active learning approaches to explain this topic, the authors constructed computer models for each student that contained the DNA corresponding to the different V, D, J, and C segments of the heavy chain of the antibody. The computer models are shown in Appendix 2. Students used their computers to see a template that had many (but not all) of the possible V, D, J, and C regions found in the heavy chain. Each student could use their computer to create their own antibody molecule by randomly selecting one segment from each of the different colored regions that corresponded to the V, D, J and C regions. They then joined the segments together to form the final antibody molecule. The different sequences chosen by each student were written on the board and the class discussed the astonishing fact that no one had the exact same sequences. It showed how the variability that was produced was inherent in the original DNA strand.

EXTENSION

For more advanced students, a similar activity can be designed to teach about how T cell receptors are made. These receptors can be divided into αβ and γδ T cell receptors. Appendix 3 shows the T cell receptor computer models. Again, the DNA sequences containing a large number of possibilities for each segment were given. Each region was shown in a different color.

CONCLUSION

Many teachers use both active learning and technology in their classes to try to engage students. One group of scientists used an inquiry-based approach to involve the students in the learning process about inflammation and molecular techniques (1). Another study looked at teaching by using active learning, team work, and technology in an introductory undergraduate biology class (3). Using the flipped classroom is another method used to engage students. It was found that the success of this method in some studies was due to the implementation of active learning in the classroom (2). In our study, we have also used technology and active learning to engage the students to learn about recombination in B cells and T cells. Students initially work independently in constructing their models and using the animation but then discuss the results as a group. We think that our approach will enhance the learning of this topic over that of an instructor simply lecturing on the material.

Appendix 1: Picture of animation used and link to animation

Appendix 2: Computer models of VDJC recombination in B cells

Appendix 3: Computer models of α, β, γ, and δ segments used in T cell recombination