B Cell Immunity Flashcards
B cell development in a fetus
- 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
Phase 1
-generation of B cells in bone marrow
Phase 2
elimination of self reactive B cells in bone marrow
Phase 3
activation of b cells by foreign antigen in secondary lymphoid tissues
Phase 4
differentiation to antibody secreting plasma cells and memory B cells in secondary lymphoid tissue
B cells in the bone marrow
- 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
Development in bone marrow and lymphoid organs
- 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
pre B cell receptor
- 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
Pre B cell
- 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
gene expression during growth
- heavy chain genes earlier and light chain genes later
- TdT decreases after heavy chains
- therefore less n regions in light chains
self-reactive B cells
- 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
bone marrow
-unrestricted repertoire of immature B cells, tolerance induction
blood and secondary lymphoid tissue
-self tolerant mature B cells and anergized (tolerant but unreactive-no T cell help) cell. additional tolerance induction
successfully enter lymphoid follicles
-long lived, mature, recirculating naive B cells (half life of 3-8 weeks
stimulation by antigen
- long-lived, mature, recirculating, memory B cells. Expression of high affinity IgG, IgA or IgE
- need some antigen stimulation to survive?
B cell response
- 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
T independent pathogens
- 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
T dependent pathogens
- 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
medullary cords
-primary focus for expansion of antigen activated B cells
germinal center
- 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
hyper IgM syndrome
- no CD40L on T cells
- no critical signal for B cells- no class switch
differentiation
- 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
