Immunoglobulin

Question 1

What’s a theory that was confirmed by Tonegawa and Hozumi about immunoglobulin diversity?

Answer 1

• two gene theory

- they analyzed Igk genes from myeloma and embryone cells to show the DNA differences

Question 2

Why did Tonegawa and Hozumi use embryonic cells to show differences in DNA?

Answer 2

• because embryonic cells dont make any antibodies

Question 3

What was the difference in Igk DNA between the myeloma cells and the embryonic cells?

Answer 3

• the Igk DNA in myeloma cell was rearranged

- the Igk DNA in the embryonic cells were the germline

Question 4

T/F: there are 2 rearrangement events for the heavy chain

Answer 4

• true

Question 5

What were the 2 versions of the light chain variable region?

Answer 5

• kappa (K)

- lambda (h)

Question 6

What was the light chain variable regions made of?

Answer 6

• a variable (V) and joining (J) gene segment

Question 7

What was the heavy chain variable region made of?

Answer 7

• variable (V), joining (J) and diversity (D) gene segments

Question 8

What’s the difference between lambda or kappa light chains? Do humans have a preference?

Answer 8

• we don’t know what the difference it
• humans are about 50/50, but other organisms have preferences for unknown reasons
• mice ~95% kappa
• sheep ~90% lambda

Question 9

When is a B cell defined?

Answer 9

• when it rearranges DNA

Question 10

What’s the difference between the physical appearance of light chain Ig locus organization vs heavy chain?

Answer 10

• in light chain all pretty similar, blocks of V’s then a J (1-5) then C
• heavy chain is similar except it has an extra gene element

Question 11

How does rearrangement lead to increased diversity?

Answer 11

• pick random combination of V D and J genes for heavy chain
• pick random combinations for light gene (lambda/kappa, V, J)
• then the total heavy and light chain combinations = over 2 million, which is more than we would get without all the cell possibilities

Question 12

What mechanisms generate the bulk of the Ig repertoire in mouse and man?

Answer 12

• combinatorial mechanisms

- making different combinations

Question 13

What’s another way to make Ig variation?

Answer 13

• junctional diversity

Question 14

Why does variation in the VDJ joint contribute greatly to Ig diversity?

Answer 14

• because this sequence corresponds to the third hypervariable loop of the V domain

Question 15

What are the 3 principle mechanisms that generate junction diversity at the time of rearrangement?

Answer 15

• junctional flexibility
• P-nucleotide addition
• N-nucleotide addition

Question 16

What part of the molecule has slightly more diversity?

Answer 16

• the part of the molecule that recognizes antigen

- helps it recognize even more