Antibody genetics

Question 1

VDJ recombination

Answer 1

-this is a mechanism by which lymphocytes create billions of unique antigen-specific receptors (BCR and TCR) from a relatively small set of genes

Question 2

VDJ is mediated by

Answer 2

RAG-1 and RAG-2

Question 3

Light chain variable regions is composed of

Answer 3

-V and J region

Question 4

heavy chain variable region composition

Answer 4

• composed of V,D, and J

- not all loci have D’s

Question 5

what is the process that makes it so we can have so many combinations of V,D, and J
-this is the initial step

Answer 5

• rearrangement of the many different genes that we have for V,D, and J regions
• these genes are mixed and matched then set together for transcription
• this is a RAG-1 and 2 dependent process and they are only expressed in B and T cells

Question 6

what do naive B cells express

Answer 6

• IgM and IgD simultaneously by alternative RNA splicing
• both of these antibodies are specific to the same antigen
• initially the antibody transcript has both classes of within the transcript but then one is removed via alternative splicing

Question 7

degrees of generation of antibody diversity

• germline
• combinatorial
• junctional
• somatic hypermutation

Answer 7

• germline: the V,D, and J genes that you inherit from your parents
• combinatorial: the way we combine our V,D and J genes during DNA rearrangement
• junctional: imprecise joining via TdT (terminal deoxyribonucleotidyl transferase_
• somatic hypermutation: this is following antigen activation as increases the affinity of the anitbody to the epitope

Question 8

somatic hypermutation

Answer 8

-this increases the affinity of antibodies to epitopes following antigen activation

Question 9

complete deficiency in RAG 1 or 2

Answer 9

results in the absence of both B and T cells and a complete loss of adaptive immunity

Question 10

class switch recombination

Answer 10

• this explains how you can take a given VDJ and change its class without changing the specificity
• after selection
• VDJ gets cut and paste in front of one of the constant regions
• plasma and memory B cells will be expressing different classes of Ig than naive B cells

Question 11

class switch recombination and somatic hypermutation
-what cells and where

Answer 11

are B cell specific mechanisms that occur during clonal expansion and selection of antigen activated B cells
-both occur in the germinal centers of the secondary lymph nodes

Question 12

activation induced cytidine deaminas

Answer 12

• found to mediate both CSR and SHM
• a defect in this enzyme results in high IgM levels and very limited class switching to IgG, A, and E, and limited production of high affinity antibodies
• def represents one form of hyper IgM syndrome

Question 13

function of class switch recombination

Answer 13

• diversifies the anitbody effector function

- makes it so the antibody can target many different pathogens in different parts of the body