B cells Flashcards
What do mature naieve B cells express?
BCR: IgM, IgD, (Iga and IgB): signaling complex Co BCR: CD19, CD81 and CR2 HLA class 1/2 CD20 CD 40
B 2 Cells
Follicular B cells (re circulating B cells) the majority
marginal B cells: reside in the spleen and attack blood borne poly saccharides
B-1 Cells
found in mucosa, limited Ag specificity
Where do naieve B cells go?
- travel to secondary lymphoid tissue if it is coming from lymphatics. Will enter through the HEV and pass through the secondary lymphoid organs.
- if it coming from blood it will go through the spleen
B cell activation: first singal
- must cross link 2 BCR -SIGNALING will then occur through the Ig alpha and beta cytoplasmic tails by ITAM (phosporylated by SYK)
- many steps occur which will make transcripton factors like Myc and NF-kB
mlg
membrane bound immunoglobulin
is crosslinking enough?
No, you need to have another signal that enances it -a bound C3d on the pathogen will bind to CR2/CD21 which will increase signaling via that receptor and CD 19 which will enahance BCR singaling: will cause proliferation and differntation.
How can you also activate b cells first singal
via TLR signaling as it recognizes pamp.
If C3d is attached to protein Ag, Ag is what?
1000x more immunogenic
what are the outcomes of the first signal
- express proteins that promote prolferation (inc prolif and survial)
- B7 is expressed which helps with T cell interaction
- increased cytokine receptors on cell
- increase expression of CCR7 (can migrate out of the follilce to T cells)
- secretion of IgM
After first activation signal what does a B cell do?
- change chemokine receptor expression and migrate to the edge of the follicular zone
- activated B cells secrete a low level of IgM and increase expression of co stimulatory molecuels and cytokine receptors to prepare for T helper cell reaction
what is the second activation singal?
-T dependent antigen: protein antigen is shown to the b cell -t independent antigen: long erpititve epitops that cross link many surface bound Igs and cause signaling
Steps of T dependent antigen activation
- recognition by membrane bound Ig of the epitope
- will endocytose the antigen and process it and express it via class 2 MHC (first step activation)
- B7 is upregulated because of the first signal and will bind to CD28 on the Th cell that is always expressed
- This will cause CD40 L to be expressed on the T cell and bind to cd40 on the B cell which is consitituvley expressed
- this will cause cytokines to be released from the T cell and activate the B cell which will cause prolieferation and expantion
ALL HAPPENS IN THE MEDULARY REGION OF THE SECONDARY LYMPHOID ORGANS
After B cells are activated by t cells what do they do. What happens in the germinal centers?
- they change their chemokine recptors and expression to mgirate to follicular areas and establish in the germinal centers in the follicules
- Class switching occurs in the germinal centers by Th cells OR they can STAY OUTISDE and become plasma cells (short lived)
What do Th cells do when they release their cytokines in the germinal cells?
- induce H chain class switching and somatic hypremuation (by AID) (occurs at the same time)
- cause cell diff and proliferation
IL4 causes what
released by t helper cells: class switching IgM to IgE and IgG 4 these protect against helminths and cause mast cell degranulation (immediate hyerseitivity)
TGF-B and April cause what
Which cause IgA formation: important in mucosal immunity
Describe switch recombilation
CD 40:CD40L ligation and cytokines trigger isotype switching by modulation of the switch region (this region is increasing the accebility of the DNA at the specific C region)
What happens after switch recomination
VDJ gene segment is attached with a new downstream c region and the rest is deleted of the DNA sequence. Thus you are not going back to your original sequence.
What does AID do?
Helps with affinity maturation: there are somatic hyper mutations that covert C to U which allows APE 1 endonuclease to make Ds breaks in the DNA of THE variable areas in the IG genes: this may be helpful but may be not.
T folicular helper cells do what?
- Will bind to activated B cells via I cos and I cos ligand (on b cell) which are essential for geminal center reactions and taken to the genminal center
- will bind CD40 and CD40L and secrete IL21 which facilates the differentiation of the B cell to a palsmablast
- then secretes ifn gamma and IL4 for cytokine switching
Steps for the selection check point
- A naieve mature b cell will be activated in the SLT
- then a Th cell will bind to it and migrate into the gernminal center and cause the indcution of AID
- the b cells are somatically mutated at V spots (hypermutation) and also constant spots (switch recombination)
- the B cell then with the high affinity antigen receptor are best able to regognize antigens of both folicular dendritic cells and antigen on TFH cell which will allow it to survive and cause it to move on and prolieferate into either plasma cells or memory cells
some will become plasma cells
Plasma cells
- Decrease of CD19,20 AND HLA class 2 markers but increase CD 27 their surface.
- They are either long or short lived and are terminally differentiated effector B cells.
- They secrete Ab at rates ranging from 100 - 1k and have an expantion of their er.
- they are effector molecules of humoral immunity
Plasma cells make what
antibodies, the effector molecule of humoral immunity.
