B Cell Immunity Flashcards
Describe the migration of mature naive B cells
Naive B cells enter the LNs across the HEV in the cortex
Slow down: L-selectin, CXCR5 (follicular chemokine receptor)
Stable arrest: LFA-1
Once in lymphoid tissue they migrate to primary follicles to sample Ags and receive survival signals from FDCs
What do mature naive B cells express on the surface?
BCR: IgM, IgD, Iga and b
Co-BCR: CD19, CD81 and CR2 (CD21)
HLA class II, CD40 and CD20
What are the two major divisions of B2 cells?
Follicular B cells which are re-circulating B cells and the majority
Marginal B cells which reside in the spleen and respond to blood borne polysaccharide Ags
Where are B1 cells located?
In the mucosa and they have limited Ag specificity
What happens if a B cell does not encounter a specific Ag in a LN?
It leaves the LN through the lymphatics and travels down the chain to the next LN
Characteristics of FDCs
Are not hematopoietic and do not process sAg or express MHC class II
They are not APCs
Express receptors for C3b (CR1) and IgG (FcyR)
Functions of FDCs
Ags are retained and concentrated in the follicles within LN by FDCs
Concentrate unprocessed opsonized Ags for naive B cells to sample for activation and activated B cells selecting of highest affinity Abs
Secrete cytokines for B cell recruitment, survival and differentiation
What are the three different mechanisms in which a first signal can be provided for B cell activation?
- Cross linking of several BCRs with signaling through Ig alpha beta ITAMs
- Cross linking of BCR with co-BCR with signaling through Ig alpha and beta ITAMs and with CR2 and CD19 signaling motifs
- Cross linking of BCR with TLRs with signaling through Ig alpha beta ITAMs and TLR signaling motifs
All three can be happening at the same time
What are the outcomes for the first signal of B cell activation?
Prepares the cell for interaction with second signal from Th cells
Receptor mediated endocytosis of BCR and Ag
Processing and presentation of Ag with MHC class II
Biochemical signaling
Increased expression of cytokine receptors
Secretion of levels of IgM
Migration of activated B cells
After activation B cells change their chemokine receptor expression and migrate to the edge of the follicular zone for interaction with activated Th cells for second signal
The newly activated T cells are also changing their chemokine receptors and moving towards the edge of the follicular zone
What changes occur in the activated B cell when it begins to migrate?
Downregulate CXCR5 and upregulates CCR7, migrates towards the paracortex, increases expression of MHC class II and B7 (CD80)
What changes occur in the T cells once they start to migrate along with the B cells that are also migrating?
Newly activated Th cells downregulate CCR7 and upregulate CXCR5, migrate towards follicles, increase expression of CD40L and cytokine secretion
What are the two ways a second signal can be provided for B cell activation?
T dependent and T independent
Explain the T dependent pathway of second signaling
Proteins
Activated CD4+ Th cell recognizes Ag displayed by B cell within MHC class II
B7 on B cell binds to CD28 on T cell
CD40L on T cell binds to CD40 on B cell
Cytokines bind to cytokine receptors on B cells
Induced expression of activation induced deaminase (AID) enzyme
Proliferation and expansion
Describe the T independent pathway of B cell activation
Everything other than proteins Mainly long repeating epitopes to be able to cross link several hundred BCRs to provide strong enough signal to bypass second signal from T cells Enough BCRs engaged to trigger enough Ig alpha and beta intracellular signaling to stimulate cell to secrete IgM No class switching, affinity maturation and little to no memory Can provide IgM Ab protection in a short amount of time
Why is B cell activation a two pronged approach (clonal selection)?
First signal: recognition of antigenic epitope by BCR
Second signal: maintains the specificity of the response to the specific epitope
This results in a large number of Ag specific plasma cells and Abs from rare Ag specific naive B cell
Describe the induction of anergy in B cells
B cells recognizing Ag without BCR cross linking, binding of co-stimulator ligands or cytokine support will not become activated
These cells become unresponsive to additional stimulus (anergic and tolerant)
Describe T follicular helper cells (Tfh)
CD4+/low levels of CD25 expression
Secrete IL-21, facilitates B cell survival, clonal expansion and differentiation into plasma cells
Secrete Th cytokines to influence isotype switching
Continued CD40L binding to B cell induction of AID
Cytokines released by Th and Tfh cells promote to general functions in B cells. What are these two functions?
- To induce heavy (H) chain class switching by opening switch regions in the heavy chain gene for somatic recombination
- To augment B cell differentiation and proliferation into plasma cells
What is the influence of IL-4 on isotype switching?
Induces IgG1 and IgE
What is the influence of IL-5 on isotype switching?
Augments production of IgA
What influence does IFN-gamma have on isotype switching?
Induces IgG3 and IgG2
What influence does TGF-beta have on isotype switching?
Induces IgG2b and IgA
Which process of B cells can only occur with T dependent Ags in which CD40/40L interaction is critical?
Heavy chain isotype switching and affinity maturation which often occur at the same time