BCR Flashcards
How many different antibodies are possible in humans?
Over 10^9 different antibodies can be produced, despite there being only ~3x10^4 genes in the human genome.
What is the structure of Ig and TCR polypeptide chains?
Consist of variable (V) and constant (C) regions.
Encoded by separate gene segments.
What gene segments encode the V regions of heavy and light chains?
Heavy chain (H) & TCRβ: V region is encoded by 3 segments: V, D, J.
Light chain (L) & TCRα: V region is encoded by 2 segments: V, J.
How does Ig gene rearrangement occur?
In B cells, DNA containing Ig gene segments is broken and rearranged during development in the bone marrow.
Non-homologous end joining recombination (NHEJ) facilitates this process.
Each B cell rearranges randomly, producing unique Ig genes.
What is the sequence of gene rearrangements during B cell development?
- Heavy chain rearranges first: D-J, then V-DJ.
- Light chain rearranges next: V-J of κ locus.
—> If unsuccessful, λ locus rearranges.
On which chromosomes are the Ig gene loci located?
Heavy chain (H): Chromosome 14
Light chain κ (L): Chromosome 2
Light chain λ (L): Chromosome 22
What mechanisms contribute to antibody diversity?
- Multiple gene segments: VH, VK, and Vλ, plus D segments for H chains.
- Combinatorial diversity: Random recombination of V, D, and J segments.
- Heavy and light chain pairing: ~2.43 x 10^6 combinations.
- Junctional diversity: Imprecise joining and random nucleotide addition.
- Somatic hypermutation (SHM): Mutation in antibody V genes during B cell activation.
What is somatic hypermutation, and where does it occur?
SHM introduces mutations into V genes of H and L chains.
Occurs in germinal centers as B cells respond to antigens.
Mediated by activation-induced deaminase (AID) enzyme.
What is the function of AID in antibody diversity?
- Deaminates cytosine to uracil, triggering error-prone DNA repair and mutations.
- Essential for both SHM and class-switch recombination.
How are Ig gene segments rearranged?
- Guided by recombination signal sequences (RSS).
- Enzymes, including RAG-1 and RAG-2, form the V(D)J recombinase complex to mediate DNA breakage and rejoining.
What ensures that each B cell expresses a single BCR/antibody?
Allelic exclusion: Only one rearranged H chain and one rearranged L chain are expressed.
Light chain isotype exclusion: A B cell expresses either κ or λ light chains, not both
How does a BCR differ from a secreted antibody?
Membrane BCR has a transmembrane region, while secreted antibodies lack it.
Both forms have identical antigen specificity due to the same rearranged VDJ regions.
How does class switching occur?
B cells switch antibody classes via DNA recombination guided by switch regions.
Requires AID enzyme, triggered by cytokines after antigen stimulation.
What determines the class of an antibody?
The constant region (C) of the heavy chain determines the class.
The order of gene segments affects class expression:
IgM is expressed first, followed by IgD, with other classes requiring further recombination.
How does junctional diversity arise?
Imprecise joining at V-D and D-J segments.
N-region addition: Random nucleotides added by terminal transferase.
