B cell activation Flashcards
Is B-cell maturation dependent on antigen?
No
ITAMs recruits
- Blk, Fyn, Lyn, which 2. causes recruitment of Syk, that dimerises and 3. activates 2nd messangers, which 4. activates transcription factors
3 things in an primary lymphoid follicle in absence of immune response
Follicular dendritic cells, antigen and B-cell attracting chemokines
Why do B cells express CCR7 in response to antigen activation?
To find cognate TFH in T-cell margin.
To make activation signal 1, a pathogen needs
Antigen recognized by BCR and complement tag recognized by CR2.
In a primary lymphoid follicle, immature and mature B cells must…
Compete for space on FDCs and BAFF.
B-cell co-receptor works as a
signal amplifier
Co-receptor mode of action
CR2 binds C3d, which causes the intracellular tail of CD19 to be phosphorylated by BCR-recruited Lyn, which starts signaling cascade.
How do FDCs store and display antigen?
Use CR1 and CR2 to bind complement proteins bound to opsonized pathogens
BAFF
Survival factor for B cells that drives maturation, produced by FDCs
How do BCRs cluster?
Repetitive antigens on microbes, lots of soluble Ag.
Germinal mantle
Cognate T-cells that came along and also divides.
Creation of germinal center
Some cognate pairs return to follicle with B cells as centroblasts and divide.
Where does cytokine activation take place?
Follicle, medulla and germinal center
Ways in which antibodies can work against pathogens
Opsonization, Complement fixation, binding to Fc-receptors on other immune cells
Centrocytes
Compete for antigen and emerges with high affinity BCR and switched Ab isotypes
Activation signal 2 is mediated by…
B cell CD40 binding to TFH cell CD40L.
Immature B cell survival depends on
Entering primary lymphoid follicles
B-cell co-receptor consists of
CD81, CD19 and CR2
AID mode of action
Deaminases cytosine to create uracil. Uracil gets replaced by a random nucleotide. Happens in the light chain
Centroblasts
Divides and mutates antigen receptors.
Where does BCR crosslinking and co-receptor binding take place?
Primary follicle
C3b opsonized antigens are bound by:
CR1 in order to catch pathogens flowing past
Plasmablast
Short-lived B-cell that are secreting IgM but still divides and interacts with cognate TFH cells.
B cell maturation take place when…
An immature B cell enter primary lymphoid follicles
Activation signal 3 is mediated by…
Binding of cytokines from TFH.
B-cell stages of development
Stem cell → Early pro-B cell → Late pro-B cell → Large pre-B cell → Small pre-B cell → Immature B cell → Mature naïve B cell → Antigen activated B cell → Centroblast → Centrocyte → Plasma or memory cell.
What happens after B cell maturation?
Mature B cells may stay and be activated or recirculate to find antigen in another follicle.
IL-21 source and function
From TFH cell, triggers proliferation of B-cell.
Types of antigens recognized by BCRs
Native antigens; proteins, lipids, sugars, nucleotide
CXCL13
B cell chemokine
BCR clustering results in
Phosphorylation of intracellular Igα and Igβ ITAMS
B-2 cells
Thymus dependent
3 B-cell antigen activation responses
Phagocytosis and processing of Ag bound to BCRs, presenting of Ag peptides on MHC II molecules for T-cells to recognize, and expression of CCR7, which causes migration toward CCL19 and CCL21 in T-cell areas.
5 improvements to B cell response that takes place in germinal center
- Clonal expansion
- Somatic hypermutation
- Affinity maturation
- Isotype switching
- Differentiation into memory or plasma cells.
Germinal dark zone
Activated B cells have become centroblasts and divide rapidly
IL-5 and IL-6 source and function
From TFH cell, trigger B lymphoblast differentiation into plasmablasts and IgM plasma calls
C3d opsonized antigens are bound by:
CR2 on macrophages and FDCs to catch pathogens as they flow past
CD40L source and function
From TFH cell. Binds CD40 on B cell and induces NF-κβ and survival factor Bcl-2. Also induce AID in centroblasts for somatic hypermutation.
How are Thymus-independent cells activated?
Binding of PAMP to eg. TLR can induce NF-κβ.
Which 3 signals activate conventional B cells?
Antigen-specifik (BCR cross-linking and co-receptor)
Co-stimulation by CD40
Cytokines (IL-21R, IL-5R, IL-6R)
B-1 cells
Thymus independent.
Where does Co-stimulation take place?
T-cell area margin
Types of antigens recognized by TCRs
Processed peptides presented in MHC
