somatic hypermutation and affinity maturation

This chemokine gradient is generated by follicular dendritic cells and recruits naive B cells that express the CCR5 receptor.

CXCL13

Activated T cells and activated B cells meet at the marginal zone of the lymph node focus because...

they both express CXCR5 and CCR7

B cells in the follicle dark zone interact with ____(1)________ and under go_____(2)____

(1) follicular stromal cells

(2) somatic hyper mutation

Somatic hyper mutation is initiated by.....

AID

Movement between the dark and light zone of the follicle is determined by expression of...

chemokine receptors 

After somatic hypermutation a B cell tests it new antibody by....

competing with older antibodies on the surface of follicular dendritic cells for the antigen found there

After somatic hypermutation B cells get a survival signal from ...

TFH cells

FDC reside and present antigen in

the margin of the light/dark zone if lymph node follicle

Activated B cells and T cells express both

CCR7 and CXCR5 and migrate to the margin 

Interactions with T cells stimulate

B cells to differentiate into plasmablasts and form a primary focus

Some T cells induce

BCL-6 and become TFH cells

B and T cell migration in the lymph node (process)

(1) before activation, resting B cells express CXCR5 and reside in follicles and T cells express CCR7 and reside in T cell zones

(2) activated B cells induce CCR7 and EBI2, and T cells induce CXCR5 and both cells migrate to follicular and interfollicular regions

(3) interactions with T cells sustain EBI2 express

Dark zone of germinal center

B cells

Light zone of germinal center

B cells and follicular T cells

Mantle zone of germinal center

where B cells interact with effector T cells

B cells in the dark zone undergo

somatic mutation of their expressed antibody variable region 

Mutation that increase the antibodies affinity for antigen lead to

capture of the antigen lead to capture of the antigen from FDC, processing and presentation to TFH cells

FDC express complement receptors and FC receptors. B cells must produce

antibodies that have higher affinity for the antigen in order to “pull” the antigen off of the FDC

TFH cells give survival signals via CD40-CD40L to those B cells that are

able to take up the antigen and then present it on MHC

Low affinity mutations lead to 

lack of survival signals and death

High affinity antibody producing clones express ______ then migrate back to the dark zone to interact with _________. They undergo additional rounds of ______ and _______.

CXCR4

follicular stromal cells

proliferation and hypermutation

B cells in the germinal center (process)

(1) B cells mutate their antibody genes in the dark zone of the germinal center

(2) B cells with high affinity for antigen can capture and process it for presentation by MHCII molecules

(3) B cells that can present antigens to TFH cells will receive survival and mitogenic signals via CD40 and cytokines

(4) B cells that receive help from TFH cells can reenter the dark zone to undergo additional mutations