Generation of Antibody Diversity Flashcards
V(D)J Recombination
A process of DNA recombination that contributes to the immense diversity of antibody and T cell receptors. Rearrangements for the variable domain of the light chain combine two gene segments, a variable segment (V) and a joining segment (J). Rearrangements for the variable domain of the heavy chain combine three gene segments, a variable segment (V), a diversity segment (D), and a joining segment (J).
Recombination-activating genes 1 and 2 (RAG1 and RAG2)
The genes encoding RAG! and RAG2 proteins, which are components of the V(D)J recombinase enzyme expressed in developing B and T cells. RAG proteins play critical roles in the DNA recombination events that form functional Ig and TCR genes. Therefore, RAG proteins are required for expression of antigen receptors and for the maturation of B and T lymphocytes.
Germline DNA
The DNA as it is inherited (from germ cells). DNA of lymphocytes is no loner germline since the genes forming either Ig or TCR have been rearranged and, in the case of Ig, possibly mutated (by somatic hypermutation) or altered by class switch recombination.
Alternative splicing
Unlike V(D)J recombination, alternative splicing occurs at the post-transcriptional RNA level, and not at the DNA level. Alternative splicing is a common mechanism and is not unique to lymphocytes. Splicing out particular exons and rejoining the RNA can form multiple variations of similar proteins.
Gene linkage
Linkage describes the tendency of genes to be inherited together due to their proximity on the same chromosome.
Gene conversion
Gene conversion is a type of genetic recombination where genetic information is shared from one DNA sequence (which remains unchanged) to another DNA sequence (which becomes altered with the new genetic material). Gene conversion is a non-reciprocal exchange of sequences. Chicken, cattle, rabbit, and sheep are so far known to utilize gene conversion to contribute to immunoglobulin diversity.
Cytokines
A range of secreted proteins of low molecular weight produced by many different cell types that exert a stimulatory or inhibitory influence on the proliferation, differentiation, and function of cells of the immune system. Cytokines are principal facilitators of communication between cells of the immune system.
Affinity maturation
A process by which B cells produce antibodies with increasing affinity for their antigen. Affinity maturation is the result of somatic hypermutation and clonal selection for cells expressing higher affinity BCR.
Combinatorial diversity
Antibody diversity resulting form the many combinations of gene segments (V, D, J) and combinations of heavy and light chains.
Class Switch Recombination (CSR)
The process by which the humoral immune response changes from being predominantly IgM to other isotypes (IgG, IgA, and IgE). Class (isotype) switching does not affect antibody specificity significantly, but alters the effector functions an antibody can engage. Class switching occurs by a site-specific recombination involving deletion of the intervening DNA.
D gene segment
Short DNA sequences that join the V and J segments in immunoglobulin heavy-chain genes and TCR-beta chains.
J gene segment
Gene segments encoding 10-15 amino acids of the variable region of immunoglobulin chains.
Junctional Diversity
Diversity is immunological receptors created during the process of joining V, D, and J segments
N-region
Nucleotides that are inserted into the junctions between gene segments in T cell receptor and immunglobulin heavy-chain V-region genes during gene segment joining. The N-nucleotides are not encoded in either gene segment, but are inserted by the enzyme terminal deoxynucleotidyl transferase (TdT). N-regions markedly increase the diversity of these receptors.
Somatic hypermutation
a mechanism unique to B cells by which point mutations are introduced into the DNA sequences encoding an antibody V-region
