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The Generation of Lymphocyte Antigen Receptors (Primary immunoglobulin…
The Generation of Lymphocyte Antigen Receptors
gene rearrangement
These are assembled in the developing lymphocyte by somatic DNA recombination to form a complete V-region sequence
Primary immunoglobulin gene rearrangement
antibody(immunoglobulin) repertoire
The total number of antibody specificities available to an individual
5-1 Immunoglobulin genes are rearranged in antibody-producing cells
somatic recombination
segments of genomic DNA within the immunoglobulin genes are rearranged in cells of the B-lymphocyte lineage, but not in other
cells.
5-2 Complete genes that encode a variable region are generated by the somatic recombination of separate gene segments
V(variable) gene segment
The first encodes the first 95-101
amino acids, the greater part of the domain
J(joining) gene segment
The second encodes the remainder of the domain (up to 13 amino acids)
D(diversity) gene segmen
heavy-chain V region才有
在V和J之間
5-3 Multiple contiguous V gene segments are present at each
immunoglobulin locus
genetic loci
κ,λ
heavy-chain loci
5-4 Rearrangement of V, D, and J gene segments is guided by flanking DNA sequences
recombination signal sequences (RSSs)
DNA rearrangements are guided by conserved noncoding DNA sequences that are found adjacent to the points at which recombination takes place
heptamer
which is always contiguous with the coding sequence, followed by a nonconserved region known as the spacer
nonamer
12/23 rule
A gene segment flanked by an RSS with a 12-bp spacer typically can be joined only to one flanked by a 23-bp spacer RSS.
5-5 The reaction that recombines V, D, and J gene segments involves both lymphocyte-specific and ubiquitous DNA-modifying enzymes.
V(D)J recombination
signal joint
The ends of the heptamer sequences are joined precisely in a head-to-head fashion to form
coding joint
The V and J gene segments, which remain on the chromosome, join to form
V(D)J recombinase
The complex of enzymes that act in concert to carry out somatic V(D)J recombination
RAG-I and RAG-2
The lymphoid-specific components of the recombinase are called RAG-I and RAG-2, and they are encoded by two recombination-activating genes, RAGl and RAG2
5·6 The diversity of the immunoglobulin repertoire is generated by four main processes
5-7 The multiple inherited gene segments are used in different combinations
5-8 Variable addition and subtraction of nucleotides at the junctions between gene segments contributes to the diversity of the third hypervariable region.
T-cell receptor gene rearrangement
Structural variation in immunoglobulin constant regions
Secondary diversification of the antibody repertoire
Evolution of the adaptive immune response