28 - B cells: B cell activation: primary focus & germinal center Flashcards
Where do all interactions happen? what happens in there? BUT.,,
Lymph node: B cell activation, differentiation, proliferation
Each step occurs in different part of lymph node
B cells migrate to different regions of lymph node during different stages
Signals direct B cells to appropriate location at each different stage (like chemokines)
Subcapsular sinus:
Where SCS macrophages are located & where they encounter Ag
outer portion of lymph node
T cell zone:
Where T cells get activated by interacting with conventional DCs
B cell zone:
Where B cells encounter Ag & undergo later stages of proliferation & differentiation
-Including B cell follicles & germinal centres can form in the follicle
T-B border
Border between B & T cell zones
-Where B cells first receive signal 2
Follicle, where is it & what happens there?
in B cell zone:
development of B cells & where they get activated
Germinal center, where is it & what happens there?
site of intense B cell proliferation & differentiation
-Can form in follicle
where in the lymph node does all signal happen?
-step by step
- B cell encounter Ag on SCS macrophage, free floating Ag OR on follicular DCs
-In B cell zone - BCR:Ag internalized & processed
- Increased expression of MHC II
- Increased expression of chemokine receptor – targets B cell to T-B border ( if TFH finds its match)
-So that follicular DC can find their match
-Where B cell receives signal 2 & become activated
B cell activation outcomes (2 Choices for activated B cells)
Form primary focus in subcapsular region
OR
Migrate to follicle to form germinal center
B cell activation, proliferation, differentiation (Steps!! for B cell activation outcomes)
- Ag encounter
-In B cell zone - B cells receive signal 1 - At T-B border
-B cell receives signal 2 (linked recognition) - B cells differentiate into Short-lived plasmablasts
-Option 1: form primary focus near subcapsular region - Germinal centre reaction
-Option 2: go to follicle to form germinal centre (GC reaction)
-B cells differentiate into Plasma cells==secrete Ab with higher affinity
Plasma cells & plasmablasts are NOT THE SAME
Naïve B cells
-Bear cell surface IgM (Membrane bound)
-Doesn’t secrete Ab
Plasmablasts
Arise from primary focus
-Differentiated B cells have begun to secrete Abs
-Can proliferate
-Still bear cell surface BCRs
Responsible for early Ab production
-IgM produced
Most plasmablasts in primary focus die by apoptosis within 5-10 days
Some can migrate to bone marrow & become plasma cells to continue Ab production
Plasma cells
Arise from germinal center reaction
-No longer proliferate (divide)
-Bear little to no cell surface Ig
-Rapidly secrete large # of Ab molecules with higher affinitity ( different classes of Ab)
-NO membrane bound BCR
Primary focus: 2 main outcomes:
Plasmablasts: early Ab production (mainly IgM -BCR on their membrane)
IgM+ Memory B cell = production of IgM Ab (Less likely)
Activated B cell that has received signals 1 & 2 migrate to form primary focus near subcapsular zone OR in interfollicular regions OR medullary cords
Activated B cells undergo proliferation & differentiate into plasmablasts
-Primary foci = apparent by ~5 days after primary infection
2nd phase: germinal center (Secondary lymphoid follicle)
2 main outcomes:
Plasma cell: secrete large quantities of Ab with higher affinity for their Ag
Memory B cell: important for memory response
-maintain capacity to produce higher affinity Ab & can secrete all classes of Ab
what happens in germinal center?
B cell receives signals 1 & 2 AGAIN
B cells undergo differentiation & processes = produce more effective & higher affinity antibodies (in the germinal center)
Size of germinal center peaks 7-12 says after Ag stimulation
-long time because it takes more time to produce more types & more effective Ab
3 processes that make B cells produce more efective Ab & have higher affinity in germinal centre
Somatic hypermutation
Affinity maturation
Class switching
what happenbs to plasmablasts?
Plasmablasts: doesn’t last long
Mostly stay I lymph node to secrete Ab
o Early Ab production
o Ab have lower affinity-Mostly IgM
what happens to plasma cells?
Either stay in lymph node(medulla)
OR travel to bone marrow & reside there & continue to produce antibodies
Produced a bit later
Higher affinity
After class switching (NOT IgM)
Both cell types can migrate to site of infection to produce Ab
After encountering antigen, stimulated B cells enter follicles, begin to divide rapidly, and undergo differentiation resulting in the formation of specialized structure called……
Germinal centers
You generate a knockout mouse that doesn’t express CD40 molecule/ On stimulation with a t-dependent antigen, do you expect this ouse to be bale to secrete IgG Ab specific for the Ag?
NO
T-dependent Ag, signal 2 is required, CD40L + CD40 is part of signal 2, it cant even form the germinal centre to make IgG
