Questions and Answers
Explain how millions of antibodies with different antigen specificities and functions are generated.
One gene codes for more than one protein via recombination. The germ line gene configuration is recombined and rearranged in individual B cells.
State why an individual B cell expresses antibody of only one specificity.
The Ig of a given B cell has a single antigen specificity because it is determined by the expression of a single rearranged heavy and light chain due to allelic exclusion.
Explain how isotype switching leads to individual B cells that produce antibodies with the same antigen specificity but with different functions.
Only the constant region has changed while antigen specificity is maintained as the same heavy chain VDJ and light chain VJ gene segments are expressed.
What is the basis for clonal selection?
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What is the role of alternate RNA processing to generate membrane vs. secreted forms of Ig?
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What is isotype switching?
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What are the five classes of immunoglobulins?
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There is an almost limitless number of potential antibodies able to recognize a vast array of antigens.
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Rearrangement occurs prior to antigen exposure in the bone marrow.
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Partial heavy chain gene rearrangement is complete in a Pro-B cell.
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At what stage of lymphocyte development does light chain gene rearrangement occur?
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As it leaves the bone marrow, B cells do not produce any Ig's.
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What are the four regions of genomic organization of immunoglobulin genes?
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Diversity in the antigen binding sites of antibodies is generated by the random recombination of gene segments.
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Explain the concept of combinatorial diversity.
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How does rearrangement (i.e., recombination) actually work? Explain the mechanism and enzymes involved in the process.
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There are two types of RAG (RAG 1 and RAG 2) and they are produced only in lymphocytes (B and T cells).
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Study Notes
Generation of B Cell Diversity
- Millions of antibodies are generated through recombination, where germ line gene configurations are rearranged in individual B cells.
B Cell Specificity
- Each B cell expresses antibodies with a single antigen specificity due to allelic exclusion; productive rearrangement of one heavy and one light chain prevents further rearrangements.
Isotype Switching
- Isotype switching allows individual B cells to produce antibodies with the same antigen specificity while changing antibody functions through alteration of the constant region without affecting the variable region.
Clonal Selection
- Clonal selection is based on allelic exclusion, ensuring that only B cells with a specific rearrangement proliferate.
RNA Processing
- Alternate RNA processing leads to the generation of membrane-bound (transmembrane) and secreted forms of immunoglobulin based on mRNA splicing mechanisms.
Immunoglobulin Classes
- There are five classes of immunoglobulins (IgM, IgD, IgG, IgA, IgE) and six subclasses (four IgG subclasses and two IgA subclasses).
Antibody Potential
- The human immune system can produce an almost limitless variety of antibodies capable of recognizing a vast array of antigens.
Gene Rearrangement Timing
- Gene rearrangement occurs prior to antigen exposure in the bone marrow, ensuring B cell readiness.
Pro-B Cell Stage
- In the Pro-B cell stage, partial heavy chain gene rearrangement occurs, while complete rearrangement is only finalized in the Pre-B cell stage.
B Cell mIg Expression
- As B cells leave the bone marrow, they express membrane-bound IgM and IgD (mIg) but do not produce secreted antibodies.
Genomic Organization of Immunoglobulin Genes
- Immunoglobulin genes have four genomic regions: variable, diversity (only in heavy chains), joining, and constant regions.
Antigen Binding Diversity
- Diversity in antibody binding sites arises from the random recombination of gene segments.
Combinatorial Diversity
- Combinatorial diversity is achieved through multiple combinations of V(D)J segments and random combinations of heavy and light chains, exceeding 1.6 million possible combinations.
Mechanism of Recombination
- Recombination involves Recombination Signal Sequences (RSS) that guide the site of recombination, facilitated by RAG proteins (RAG-1 and RAG-2) that are specifically produced in lymphocytes.
RAG Proteins
- RAG-1 and RAG-2 only function in lymphocytes (B and T cells) to mediate V(D)J joining through DNA looping and cleavage.
Additional Diversity Factors
- While combinatorial diversity contributes to antibody specificity, it does not encompass all the diversity in antibodies. Other mechanisms also play a role.
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Description
Explore the intricate mechanisms behind B cell diversity in antibody generation. This quiz focuses on the processes of gene recombination and the specificity of antibody expression in individual B cells. Test your knowledge with key definitions and explanations related to immunology concepts.
