Lecture 4 Adaptive Immunity - B Cell Development

Question 1

How are endogenous and exogenous antigens presented?

Answer 1

Endogenous antigens presented with MHC II

Exogenous antigens presented with MHC I

Question 2

Go through BCR Mechanism

Answer 2

BCR on B cell recognized native antigen

• antigen causes intracellular signalling and activation
• antigen internalized and processed into peptides
• peptide presented with MHC II to Helper T cell

Question 3

What is the TCR?

Answer 3

Antigen presenting cell presents processed antigen, peptides, with either MHC I or MCH II to TCR

Question 4

What are the regions and parts of a BCR? Both surface and antibody.

Answer 4

Question 5

What are the regions and parts of the TCR?

Answer 5

Question 6

What is the difference between the Surface Immunoglobulin and an antibody?

Answer 6

The antibody has no transmembrane region

Question 7

How many antigen binding sites are present on a BCR and a TCR?

Answer 7

BCR has 2 antigen binding sites

TCR has 1 antigen binding sites

Question 8

How do the different antigen binding sites differ in BCRs and TCRs?

Answer 8

The amino acid sequence of the polypeptide chains differ causing the antigen binding sites to be different

Question 9

What are the parts of the immunoglobulin, Ig, structure? Ig are antibodies.

Answer 9

Question 10

What is the Fab on an Ig?

Answer 10

Fab stands for Fragment of Antigen Binding

-this is the antigen binding site

Question 11

What is the Fc on an Ig?

Answer 11

Part that is recognized by and interacts w/ rest of immune system

• doesn’t bind antigen
• phagocytic clls have FcR which bind part of antibody to phagocytoze
• adaptive and Innate interaction
• Different Isotypes= IgA, IgD, IgE, IgG, IgM

Question 12

What are the different Ig Isotypes?

Answer 12

Question 13

What are the regions of the Ig?

Answer 13

Each chain has a variable and constant region

-since each chain is a polypeptide chain that means there are genes for heavy and genes for light chains

Question 14

What are the heavy chain gene segments and how many of each are there?

Answer 14

Variable Region

V_1-41 - D_1-23 - J_1-6 - C

Constant Region

Cµ, Cd, Cg, Cα, or Cε

Question 15

What are the light chain gene segments?

Answer 15

Variable region

V_1-41 - J_1-5

Constant region

C_k or C_l

Question 16

Can’t have a gene for every pathogen out there, how do we address this issue?

Answer 16

Gene Rearrangement

• After hematopoiesis but before maturing the genes for heavy/light chains rearrange
• each mature lymphocyte has same Constant region
• each mature lymphocyte has one V, D, J gene in Variable region

Question 17

What is the downside of gene rearrangement?

Answer 17

You end up making alt of antigen binding sites that don’t bind anything

• waste of energy
• do it enough times you get some working ones

Question 18

How many possibilities are created by gene rearrangement (recombination)?

Answer 18

2. 09 x 10⁶ possibilities
   - Heavy chain V-D-J recombination
   - Light chain V-J recombination
   - H-L=antigen binding site

Question 19

What enzyme make recombination possible? What is its job?

Answer 19

Recombinase-activating gene (RAG) endonucleases

-RAG randomly cuts out V-D-J segments and sticks together

Question 20

How do we create more than just 2x10⁶ possibilities for different antigen binding sites?

Answer 20

Junctional diversity

• the enzymes Artemis and TdT add random nucleotides at junction sites between variable regions
• creates frameshift mutations leading to new possibilities

Question 21

What if someone is born with a RAG deficiency?

Answer 21

They will have no antigen-binding site diversity resulting in an inability to fight infection

They will not be able to make BCRs or TCRs w/o RAG

-resulting in not functional B cells or T cells

Question 22

Walk through B-cell development.

Answer 22

Progenitor B cell expresses heavychain first (D-J-V)

• to see if H-chain is functional its tested with surrogate light chain to form the Pre-BCR
• if non-functional it gets 2nd chance with 2nd allele
• if still non-functional then apoptosis

Light chain is expressed (K-λ)

• μ+K are expressed first
• if K is productive then expressed, if not 2nd K allele tried
• if K alleles unproductive then λ alleles tried
• if any are productive then they are kept or else apoptosis

Once functional Lymphocyte with IgM or IgD BCR is created then move on to negative selection

Question 23

What is positive selection and negative selecion in B cell development?

Answer 23

Positive selection is when you have a functional productive allele it moves on to the next checkpoint

Negative selection is when a BCR binds to self antigens in bone marrow while maturing then it will be killed or undergo receptor editing

Question 24

What is negative selection in detail?

Answer 24

Immature B cells with BCR in bone marrow interacts w/ cells/antigens

• If BCR encounters/interacts w/ antigen it will be self which is a sign of autoimmunity
• If B-cell binds antigen then either apoptosis or receptor editing
• receptor editing are genetic changes at the V-D-J level
• If not antigen binding then the B-cell will mature and move to secondary lymphoid tissue