INTRODUCTION

One of the key features of the immune system is that it can defend the body against a great diversity of invaders. It is capable of recognizing millions of molecular features, called antigenic determinants, which any invading organisms or molecules might display.

Some of the immune system's power to respond to this diversity comes from the action of certain protein molecules, called antibodies or immunoglobulins. Each of the millions of B cells in the immune system produces a unique type of antibody. Each unique antibody, in turn, can bind to a particular antigenic determinant. When a B cell develops from a precursor cell into a mature cell, it undergoes an unusual genetic process in which it rearranges its immunoglobulin genes. DNA segments are randomly rearranged and joined, and some DNA is permanently deleted. The resulting immunoglobulin genes are unique and code for the unique antibodies that each mature B cell produces.

Before a B cell can produce antibodies (immunoglobulins), the genes that encode the light and heavy chains must undergo a rearrangement process. These genes rearrange while a B cell is immature, in a stage called a B cell precursor.

CONCLUSION

We can account for most of the diversity of antibodies in the immune system by considering the immunoglobulin gene rearrangement process. The amino acid sequence of the variable region (which is encoded by a V, D, and J segment) is different for each specific immunoglobulin and is responsible for antibody specificity. The DNA segments within the heavy chain gene are rearranged and joined to produce a gene with a variable region that includes one V, D, and J segment. In mice, there are 100 V, 30 D, and 6 J segments to choose from. Therefore, the number of different heavy chain variable regions that can be made through a random rearrangement process is quite large: 100 × 30 × 6 = 18,000.

Now consider that the light chains are constructed with a similar amount of diversity, also made possible by random recombination. If we assume that light-chain diversity is the same as heavy-chain diversity (18,000 possibilities), the number of possible combinations of light and heavy chains is 18,000 unique light chains × 18,000 unique heavy chains = 324 million possibilities!

Even if this number is an overestimate by severalfold (and it is), the number of different immunoglobulin molecules that a B cell can make is huge. In addition to the random recombination process, there are several other mechanisms that generate additional diversity. For example, during the rearrangement process, the segments are often joined imprecisely, which introduces slight changes to the coding regions of the joined segments. Considering all the mechanisms for generating unique antibodies, it is not surprising that the immune system can mount a response to almost any natural or human-made substance!

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Textbook Reference: Concept 39.4 The Adaptive Humoral Immune Response Involves Specific Antibodies