Antibody Gene Recombination and Hypermutation

B cell maturation

happens in the bone marrow

T cell maturation

happens in the thymus

Heavy Chain

VH,CH1,CH2,CH3

Light chain

VL,CL (kappa) or CL (lambada)

TCR are made up of diverse

alpha and beta chains

Recombination of VJ

leads to diverse LLs if recombined leads to increased diversity

Recombination of VDJ

leads to diverse HCs the recombination of which leads to increased diversity

B cell activation steps

somatic hypermutation, affinity maturation, and isotype class switch

Mutations with hypervariability regions=

BCRs with increased affinity for antigen

During antigen driven B cell expansion there is preferentially stimulated to produce

high affinity antibodies

B cells improve the quality of

antibodies during infection

Hypervariable regions

complementarily determining regions within the Fab and HC and LC

Affinity Maturation

-clones of B cells are not perfect

-B cells have the opportunity to bind to pathogens

cloning of b cells=

high mutation rates (somatic hypermutation)

somatic hypermutation can result in

daughter cells that have different receptors from the parent

If B cells have a high affinity for a pathogen they will be

activated and cloned

increased affinity B cell have for a pathogen that is present=

increased likelihood that the B cell will survive

variation provided by

hypermutation

selection provided by

competition for pathogen

Disadvantage of mutation of B cells

apoptotic B cell

As population of B cells undergoes affinity maturation

This generates B cells with a higher pathogens affinity (these B cells are more efficient at detecting and capturing pathogens)

Somatic hypermutation of V genes occurs in

germinal centers

Hc variable region

contains additional diversity CDR1,CDR2,CDR3

CDR3

most variable region (on either side of the D segment, the CDR3 regions are variable N regions)

N regions are generated by

deleting a few bases and than adding a random sequences )=hypervariable)

The effects of booster baccination on antibody levels and affinity

-For antibody level and affinity IgG and IgM increases with boosters (biggest increase happens between second and third shots)