L10 Flashcards
What Ab dominates primary exposure response to antigen? Secondary exposure?
Primary - IgM
Secondary - IgG or whatever isotype was selected for that pathogen in making memory cells (parasitic worms = IgE)
What parts of somatic diversification of B cells happens at the bone marrow? Describe it.
VDJ Recombination
- immature B cells ONLY
- RAG 1/2
- Antigen INDEPendent
1. Heavy chain recomb (allelic exclusion if needed)
2. Light chain (receptor editing if needed)
What parts of somatic diversification of B cells happens in secondary lymph organs?
- Somatic hypermutation
- Class switch recombination
- Both AID dependent
- MATURE B cells only
- Antigen dependent
What is SHM?
= affinity maturation
Point mutations made to heavy or light chain VARIABLE regions
- Where CDRs are coded
What is CSR?
= isotype switching
Recombination of HEAVY C genes
What chemokine receptor gets upregulated in naive B cells for movement to secondary lymph organs?
CCR7
What chemokine receptor gets upregulate in B cells to move into circulation/out of lymph organs?
CXCR5
What is the difference between how DC in T cell zones vs FDCs are made?
DC in T cell zones - from hematopoietic precursors
FDC - derived @ lymph node
What is the TAPPA receptor on B cells? What happens when this is bound?
CD19 + CD81 + CR2 (CD21)
Complement receptor
Signals via PI3 kinase
Lowers threshold of activation for B cell
Which cell surface molecule is distinguishing for B cells?
CD19
Which complement does CR2 bind?
3d & i3b
What 3 things happen after a B cell binds its BCR in the periphery?
Acts as an APC - phagocytosis of receptor + antigen
- Mitosis –> clonal expansion
- ↑CCr7 to move to lymph nodes
- Low level IgM secretion
Why are antigen-specific B cells more likely to receive help from antigen-specifc T cells?
CONCENTRATION EFFECT
APC property of B cell to present on MHC2
How do you mount an immune response with memory against carbohydrates?
Couple with protein carrier
Alone would get B cell stimulation - but no memory
What is the difference between a primary vs secondary lymphoid follicle?
Secondary has germinal center!
How do Ab-antigen-complement complexes stimulate a response in the lymph node?
Enter via subcapsular sinus
Macrophages with CR3 bind iC3b molecules
Macrophages phagocytose the complex - present to naive B cells in follicle
Naive TAPPA complex binds
Passes complex to FDCs - present antigen on Fc gamma receptor or CD21
Antigen binds specific B cell
What happens once a specific B cell has bound an antigen-complement complex presented by FDC?
↑CCR7 to move to T/B border
↑CXC5 production (chemokine) to pull the T cells to the border too
↑CD40 expression for co-stimulation
What are the 2 paths that a B cell can take after meeting a T cell at the follicle border?
- T cell saw B cell with high affinity receptor - good to go! Become a plasma cell and secrete those Abs
- T cell saw B cell that needs a better BCR
- ↑CCR7 –> back into germinal center
- CSR & SHM
What 2 signals are needed to determine the recombination fate of B cells needing more maturity?
CD40L & appropriate cytokine
Upregulates AID
Cytokines det which switch boxes open for recomb of VDJ gene
What cytokine induces IgG B cells?
IFN gamma
What is the primary role of IgGs?
Opsonization for phagocytosis
What is the primary role of IgM?
Complement activation
What cytokine induces IgE B cells?
IL4
What cytokine induces IgA B cells?
TGF beta - those produced by mucosal tissues
What is the germinal center reaction?
@ light region of germinal center
Switched B cells present new receptor to FDCs to see if they pass the self test
Yes –> plasma/memory cells
No - anergy/apoptosis
What are centroblasts?
Dark region of germinal center
Where B cells are undergoing SHM and CSR
Cell division!!!
What are centrocytes?
Where B cells in germinal center have stopped dividing
Undergoing the germinal center reaction
What causes type 2 hyper IgM syndrome? Give symptoms.
AID deficiency due to inactivating mutation
Symptoms: repeated bacterial infections
WHAT IS THE CLASSIC HISTO FINDING for type 2 hyper IgM syndrome?
Histo: ENLARGED GERMINAL CENTERS
- Send B cells here for SHM & CSR but can’t do anything about it!
- Only get primary IgM response from B cells - no class switching
What causes type 1 hyper IgM syndrome? Give symptoms? What is the primary histo finding?
CD40/CD40L mutations
No T-B cell interaction –> never send anything to GC
NO GERMINAL CENTER FORMATION ON HISTO
High IgM but no other isotypes
Same symptoms as type 2 - repeated bacterial infections
