7/8: Antibody diversity and B cell development Flashcards
how is the antigen binding pocket formed
- junction of the heavy and light chain variable regions
- rearrangement of chromosomal DNA to create the exon encoding it
how does each b cell make a unique receptor
rearrangement and mutation of the germline DNA
what is the only isotype generated at first
IgM
what is tolerance
absence of immune response to own antigens
steps in B cell development
- generation of b cell receptors in bone marrow
- negative selection in the bone marrow
- migration of b cells to peripheral lymphoid organs and activation
- antibody secretion and memory cells in bone marrow and lymphoid tissues
how does each b cell develop receptors (antibodies) that can bind to a single epitope different than the epitope recognized by other b cells
during development in the bone marrow –> splicing its chromosomal DNA to create new coding sequences for the antigen binding pocket exon
how is the region of the antibody gene that binds the epitope generated
by a semi-random rearrangement and combining of gene segments –> different exons for the antibody chains within each b cell
multiple germline gene exons
both heavy and light chains may be encoded by multiple variable region DNA segments that are spliced together to form the variable region exon
H and L chain combinations
the antigen binding site is formed by the interaction of both chains, and any given H chain can dimerize with any given L chain
imprecise joining of segments
during somatic rearrangement, the gene segments for a variable region can be spliced together using any of several nucleotides
random insertion of bases
during splicing, nucleotide bases can be randomly inserted into the splice junction, thereby changing the codon frame
somatic hypermutation
areas within the variable regions which are subject to germline base substitutions during cell division –> the only diversity mechanism that occurs after a b cell encounters its specific antigen
what has to happen for a b cell to survive and leave bone marrow
successful rearrangement of both heavy and light chain genes
multiple germline genes
- many different gene segments and permits rearrangement
- great diversity can be achieved
H-L chain combinations
- heavy chain rearranges independently of the light chain
- by combining different H and L chains, each with own variable region rearrangements, can generate antigen binding pockets of various specificity
3 regions in antibody genes
V, D, and J segments (plus constant region exons)
VDJ gene rearrangement
bringing segments together through splicing
imprecise joining (junctional flexibility)
- arbitrarily splicing nucleic acids together within a region –> different reading frames generated –> different amino acid structure at the antigen binding pocket
- occurs at all VDJ junctions during recombination
random base insertion (or P nucleotide addition)
- during recombination of VDJ segments, nucleic acids can be randomly inserted into the junction
- generates a different amino acid structure at the antigen binding pocket
what is allelic exclusion
-rearrangement of the antibody gene DNA is a random event that occurs only on one chromosome for each heavy or light chain genes
what does allelic exclusion assure
that each individual b cell generates only a single antibody molecule rather than expressing the genes from both chromosomes (each b cell produces identical antibodies)
does the heavy or light chain rearrange first
heavy chain, then light chain
does the choice of heavy chain VDJ region influence which light chain V and J regions will be selected
no
what does RAG stand for
recombination activating genes
