The importance of genetic recombination and post recombination events related to diversity in antibodies Concept introduction: Antibodies are the potential receptors that can recognize unique aspects of antigen present on the pathogen. Antibodies are produced by the differentiation of B cells into plasma cells. Based on the physical, chemical, and immunological properties, antibodies are classified into 5 classes namely IgG, IgA, IgM, IgE, and IgA. All the antibodies share a common structural similarity by having 2 light and 2 heavy chains. Each light and heavy chain are further classified into “constant (C) and variable (V) domains”. Disulphide bonds connect one light chain with another heavy chain. Each heavy and light chain is derived from the combination of several gene fragments generated after several events of recombination.

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Chapter 27, Problem 2AQ

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The importance of genetic recombination and post recombination events related to diversity in antibodies

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Antibodies are the potential receptors that can recognize unique aspects of antigen present on the pathogen. Antibodies are produced by the differentiation of B cells into plasma cells. Based on the physical, chemical, and immunological properties, antibodies are classified into 5 classes namely IgG, IgA, IgM, IgE, and IgA. All the antibodies share a common structural similarity by having 2 light and 2 heavy chains. Each light and heavy chain are further classified into “constant (C) and variable (V) domains”. Disulphide bonds connect one light chain with another heavy chain. Each heavy and light chain is derived from the combination of several gene fragments generated after several events of recombination.

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The diagram in the first figure shows simplified versions of the immunoglobulin heavy chain locus, the T-cell receptor b chain locus, and the locus encoding the RAG-1 and RAG-2 recombinases. For the sake of this question, imagine that these diagrams represent all of the gene segments present in the immunoglobulin heavy chain and T-cell receptor b chain locus. You now analyze five individuals, each of which has a single inactivating mutation in a region of one of these three loci. These mutations are each indicated by a red ‘X’ in the second figure, and are numbered 1–5. For each of these inactivating mutations, indicate the alterations and/or defects that would be seen in the repertoire of antigen receptors found in mature B and T cells in that individual. Also, for each mutation, indicate whether the individual would likely show any immunodeficiency, such as a history of recurrent infections.

In a particular species, the gene for the kappa light chain has 200 V segments and 4 J segments. In the gene for the lambda light chain, this species has 300 V segments and 6 J segments. If only the antibody diversity arising from somatic recombination is taken into consideration, how many different types of light chains are possible?

Suppose that a particular species of vertebrate animal has immunoglobulin heavy-chain genes that include 55 V segments, 21 D segments, and 8 J segments, and has immunoglobulin light-chain genes that include 41 V segments and 6 J segments. How many different immunoglobulin structures could be produced by mature B-lymphocytes? (Assume that segments are spliced without any junctional variation or imprecision).