Antibody Diversity Flashcards
What is the clonal selection hypothesis?
Lymphocytes express antigen receptors before encountering antigens and antigens select and activate specific lymphocytes to proliferate
What triggers B cell activation?
Antigen binding to immunoglobulin receptors IgM or IgD on the B cell surface
What is somatic recombination?
The rearrangement of immunoglobulin gene segments to generate diverse antibodies with unique specificities
Where does somatic recombination occur?
In the bone marrow and it is antigen-independent
What segments are involved in heavy chain recombination?
V variable D diversity J joining and C constant segments
What segments are involved in light chain recombination?
V variable J joining and C constant segments
What is the first step in somatic recombination for heavy chains?
D and J segments are joined first followed by joining of the V segment to the D-J complex
What is the 12/23 rule in recombination?
Gene segments can only join if one has a 12-bp spacer and the other has a 23-bp spacer
What enzymes control somatic recombination?
Recombinase-activating genes RAG1 and RAG2 and DNA repair enzymes
How does RAG recognize gene segments for recombination?
By binding to recombination signal sequences RSS near the V D and J segments
What happens after RAG enzymes cut the DNA?
The cut DNA forms a hairpin loop which is cleaved and processed by other enzymes to add/remove nucleotides (which introduces more diversity) and join segments
What is the result of successful somatic recombination?
A functional variable region gene for an antibody, heavy / light chain is formed
What happens if RAG proteins are defective?
Partial defects cause Omenn syndrome while complete absence results in Severe Combined Immunodeficiency SCID
What is junctional diversity?
Diversity created by imprecise cutting during recombination adding or losing nucleotides at joining sites
What is the role of TdT terminal deoxynucleotidyl transferase?
Adds random nucleotides to DNA during heavy chain recombination increasing diversity
What is the cost of junctional diversity?
Imprecise joining can create non-functional sequences leading to B cell apoptosis
How are non-functional antibody genes handled?
Frame shifts or non-productive rearrangements result in apoptosis of the B cell
What is the role of recombination signal sequences RSS in recombination?
They guide RAG enzymes to ensure proper V D and J segment joining
What happens after the heavy chain successfully rearranges?
The light chain undergoes recombination starting with kappa and if needed lambda chains
How do B cells express antibodies on their surface and what happens to non functional antibody B cells?
The rearranged heavy and light chains are expressed as IgM on the cell surface and non-functional combinations lead to apoptosis
What is RNA splicing in B cells?
A process that occurs at the RNA level which splices antibody RNA which enables the expression of IgD (with IgM) with the same antibody specificity as the original IgM on the surface of naïve B cells
What are the components of the antigen-binding site in antibodies?
Formed by the variable regions of the heavy and light chains
How does somatic recombination follow an ordered process?
Heavy chains rearrange first followed by kappa or lambda light chains
What is apoptosis in the context of antibody diversity?
Self-reactive or non-functional B cells undergo programmed cell death to prevent autoimmunity
How do heavy and light chain recombinations differ?
Heavy chains involve V D and J segments while light chains only use V and J segments
What is the significance of the DNA repair process in recombination?
Ensures proper joining of V D J segments and contributes to diversity through junctional modifications
