B cells: Antigen Recognition

Question 1

what are the main isotypes of antibody?

Answer 1

IgD
IgM
IgG
IgA
IgE

Question 2

what is the structure of antibody?

Answer 2

Two H-chains
Two L-chains divided into constant and variable regions

Question 3

what are the two types of L-chains?

Answer 3

Kappa or lambda

Question 4

what is the human ratio of kappa to lambda in humans?

Answer 4

kappa:lambda
2:1

Question 5

what are CDR of antibody?

Answer 5

Complementarity Determining Regions

Question 6

what is the function of CDRs?

Answer 6

CDR are the main points of contact to antigen
They are hypervariable

Question 7

where are CDR located in antibody?

Answer 7

L-chains and H-chains contain three CDR each

Question 8

what CDR regions are within the light chain?

Answer 8

CDR1
CDR2
CDR3

Question 9

what encodes the CDR light chain areas?

Answer 9

V gene encodes CDR1 and CDR2
V/J genes encode CDR3

Question 10

what CDR regions are within the heavy chain?

Answer 10

CDR1
CDR2
CDR3

Question 11

what encodes the CDR heavy chain areas?

Answer 11

V gene encodes CDR1 and CDR2
V/D/J genes encode CDR3 (these have additional diversity as they have messy joins

Question 12

what is the most CDR variable region?

Answer 12

CDR3 is the most variable region because it is present at V-D-J or V-J junctions

Question 13

what generates diversity in B cells?

Answer 13

TCR beta undergo V-D-J rearrangements. These occur before TCR alpha rearrangement.
TCR alpha have V-J rearrangements. These occur after TCR beta rearrangements.

Question 14

what generates Fc and Fab antibody regions?

Answer 14

Cleavage by the papain protease gives distinct fragments called Fc and Fab

Question 15

what is the role of Fab?

Answer 15

Fab is involved in antigen binding

Question 16

what is the Fc region?

Answer 16

Fc defines a portion that binds to Fc receptors

Question 17

what is the role of Fc receptors?

Answer 17

FcR can trigger NK cell, macrophage and DC activation. FcR stimulate antigen uptake and complement activation

Question 18

why are antibodies flexable?

Answer 18

Due to a hinge region that allows them to recognise widely or closely spaced surface determinants

Question 19

how are antibody hinge and constant domains used in the lab?

Answer 19

Commonly used in the lab as a scaffold for protein expression

Question 20

how are B cells activated?

Answer 20

-mediated by CD4 T cells
-Thymus independent (TLR and Ig crosslinking)

Question 21

what is Thymus-dependent B cell activation?

Answer 21

TD is T helper cell mediated activation of B cells. Normally mediated by CD40L and IL-4

Question 22

what is Thymus-independent B cell activation?

Answer 22

TI occurs when BCR is crosslinked and when string TLR signalling occurs

Question 23

what does thymus-independent antigen?

Answer 23

Normally low affinity IgM antibodies are produced. Often recognise lipids and carbohydrates

Question 24

what antibody do naive B cells express?

Answer 24

IgM and IgD as membrane-bound forms

Question 25

how much more likely are B cells to be specific?

Answer 25

B cells producing antibody specific for a given antigen are 10,000x more likely to bind and internalize specific antigen

Question 26

what do conventional TD B cells need to produce antobody?

Answer 26

Two antigen-specific lymphocytes that present guards against unwanted B cell activation (autoimmunity)

Question 27

why do non activated B cells have low affinity antibody?

Answer 27

Their antobody is IgM and of low affinity so is unlikely to cause autoimmunity

Question 28

what does activation of TI B1 cells in the absence of microbial signalling do?

Answer 28

Induces tolerance and deletion