B cells: Antigen Recognition Flashcards
what are the main isotypes of antibody?
IgD
IgM
IgG
IgA
IgE
what is the structure of antibody?
Two H-chains
Two L-chains divided into constant and variable regions
what are the two types of L-chains?
Kappa or lambda
what is the human ratio of kappa to lambda in humans?
kappa:lambda
2:1
what are CDR of antibody?
Complementarity Determining Regions
what is the function of CDRs?
CDR are the main points of contact to antigen
They are hypervariable
where are CDR located in antibody?
L-chains and H-chains contain three CDR each
what CDR regions are within the light chain?
CDR1
CDR2
CDR3
what encodes the CDR light chain areas?
V gene encodes CDR1 and CDR2
V/J genes encode CDR3
what CDR regions are within the heavy chain?
CDR1
CDR2
CDR3
what encodes the CDR heavy chain areas?
V gene encodes CDR1 and CDR2
V/D/J genes encode CDR3 (these have additional diversity as they have messy joins
what is the most CDR variable region?
CDR3 is the most variable region because it is present at V-D-J or V-J junctions
what generates diversity in B cells?
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.
what generates Fc and Fab antibody regions?
Cleavage by the papain protease gives distinct fragments called Fc and Fab
what is the role of Fab?
Fab is involved in antigen binding
what is the Fc region?
Fc defines a portion that binds to Fc receptors
what is the role of Fc receptors?
FcR can trigger NK cell, macrophage and DC activation. FcR stimulate antigen uptake and complement activation
why are antibodies flexable?
Due to a hinge region that allows them to recognise widely or closely spaced surface determinants
how are antibody hinge and constant domains used in the lab?
Commonly used in the lab as a scaffold for protein expression
how are B cells activated?
-mediated by CD4 T cells
-Thymus independent (TLR and Ig crosslinking)
what is Thymus-dependent B cell activation?
TD is T helper cell mediated activation of B cells. Normally mediated by CD40L and IL-4
what is Thymus-independent B cell activation?
TI occurs when BCR is crosslinked and when string TLR signalling occurs
what does thymus-independent antigen?
Normally low affinity IgM antibodies are produced. Often recognise lipids and carbohydrates
what antibody do naive B cells express?
IgM and IgD as membrane-bound forms
how much more likely are B cells to be specific?
B cells producing antibody specific for a given antigen are 10,000x more likely to bind and internalize specific antigen
what do conventional TD B cells need to produce antobody?
Two antigen-specific lymphocytes that present guards against unwanted B cell activation (autoimmunity)
why do non activated B cells have low affinity antibody?
Their antobody is IgM and of low affinity so is unlikely to cause autoimmunity
what does activation of TI B1 cells in the absence of microbial signalling do?
Induces tolerance and deletion
