B Cell Immunity

Question 1

B cell development in a fetus

Answer 1

• location of hematopoiesis is in the liver
• liver remains the major site of fetal hematopoiesis until shortly before birth when stem cells travel by blood to the spleen and bone marrow
• population of the bone marrow may be facilitated by chemotactic and growth factors released from the bone matrix and CT cells

Question 2

Phase 1

Answer 2

-generation of B cells in bone marrow

Question 3

Phase 2

Answer 3

elimination of self reactive B cells in bone marrow

Question 4

Phase 3

Answer 4

activation of b cells by foreign antigen in secondary lymphoid tissues

Question 5

Phase 4

Answer 5

differentiation to antibody secreting plasma cells and memory B cells in secondary lymphoid tissue

Question 6

B cells in the bone marrow

Answer 6

• produced by bone marrow every day throughout life
• 2.5 billion cells/day start on the path towards becoming a B cell
• 55 billion cells/day die because they fail to productively rearrange immunoglobulin or are autoreactive
• 30 billion cells/day leave the bone marrow

Question 7

Development in bone marrow and lymphoid organs

Answer 7

• go through all gene rearrangements and leave bone marrow
• goes into circulation
• needs to get into lymph node to survive- will die in 3 days if not or become anergic
• also needs to see antigen
• if activated, aide comes in and does somatic hypermutation to select for best antibody-then class switch and memory cells

Question 8

pre B cell receptor

Answer 8

• has a surrogate light chain to make sure the antibody can fold correctly
• if it’s not folded properly, there won’t be a transmembrane domain and signal and the cell will die
• if folded properly-signal-division and then light chain rearrangements

Question 9

Pre B cell

Answer 9

• rearranged heavy chain but a surrogate light chain
• signals:
• end of heavy chain rearrangement
• cell survival
• cell proliferation
• then light chain rearrangement commences
• 2 checkpoints- this one that checks for heavy chain functionality and another for light chain

Question 10

gene expression during growth

Answer 10

• heavy chain genes earlier and light chain genes later
• TdT decreases after heavy chains
• therefore less n regions in light chains

Question 11

self-reactive B cells

Answer 11

• if not self reactive, leaves and goes to the blood and expresses IgD and IgM
• retained in bone marrow if self reactive
• given a chance to rearrange again
• if better second time goes to blood
• if not will always be self reactive and dies

Question 12

bone marrow

Answer 12

-unrestricted repertoire of immature B cells, tolerance induction

Question 13

blood and secondary lymphoid tissue

Answer 13

-self tolerant mature B cells and anergized (tolerant but unreactive-no T cell help) cell. additional tolerance induction

Question 14

successfully enter lymphoid follicles

Answer 14

-long lived, mature, recirculating naive B cells (half life of 3-8 weeks

Question 15

stimulation by antigen

Answer 15

• long-lived, mature, recirculating, memory B cells. Expression of high affinity IgG, IgA or IgE
• need some antigen stimulation to survive?

Question 16

B cell response

Answer 16

• they see surfaces
• can’t see antigen with MHC they need it alone
• antigen brought in in circulation
• also thought DCs keep some whole antigens

Question 17

T independent pathogens

Answer 17

• can stimulate B cells without T cell help
• via toll receptors
• no memory
• for bacteria-brucella and salmonella-LPS and LOS-TI1 and 2
• B cells still have toll receptors-make antibodies to bacteria
• can make Ig for LPS, components of bacteria in the presence of LPS, or whole bacteria via it’s DNA (uses TLR9 not 4)
• TI-2 uses many cross linked antibodies to activate B cells

Question 18

T dependent pathogens

Answer 18

• naive CD4 t cells activated by antigens presented by DCs-T cell first because adjuvents go to T cells
• naive B cells are activated by antigen and trapped in the T cell zone of lymph node
• antigen-activated B cells present antigen to helper t cells (with MHC class II, CD40 and CD40L (on T cell),CD28-B7, cytokines) form a cognate interaction and conjugate pairs (immune synapse)
• cytokines released in very close spaces because T cell reorients cytoskeleton

Question 19

medullary cords

Answer 19

-primary focus for expansion of antigen activated B cells

Question 20

germinal center

Answer 20

• secondary focus for expansion of antigen activated B cells, most expansion here
• T cells help B cells divide
• follicular dendritic cells (not regular dendritic cells-just has dendrites) present antigen for B cells
• activated B cell reacts with T cell
• somatic hypermutation of Ig region in proliferating germinal center centroblasts occurs (AID, also helps with class switching)
• B cells with high affinity Ig cross link to T cell and proliferate
• T cell also gives signal for class switch

Question 21

hyper IgM syndrome

Answer 21

• no CD40L on T cells

- no critical signal for B cells- no class switch

Question 22

differentiation

Answer 22

• IL10 secreting T cell differentiates B cells into plasma cells
• IL4 secreting T cell differentiates B cells into memory B cells
• resting B cells have MHC class II while plasma cells do not