B cell development
Explain the image
B cell enters secondary lymph tissue via blood vessel, and moves to B cell area. If it gets trapped in the T cell area it dies. If it is not activated it moves on to the next secondary lymph tissue
What cells can be activated to produce antibody against two types of antigens?
B cells
What are the two major B cell populations?
B1 and B2
Which rearrangement happens first? H-chain or L-chain?
H-chain
where can elimination of self-reactive B cells occur?
In the bone marrow or outside the bone marrow
What can antibody effectors do?
Neutralizing antibodies against microbial toxins and animal venoms (independent of Ig isotype) Opsonization (phagocytosis) - IgG specific Fc receptors ADCC - IgG binds to tumor or virally infected cell and can be killed Complement activation - IgG and IgM IgM more efficient IgE receptors on mast cells, basophils and activated eosinophils Rapid rejection of pathogens, e.g. parasites Allergies (Type I hypersensitivity)
After activation where do B cells migrate to?
Primary follicle
What proteins are required for region rearrangements>
RAG
Where are T dependent responses developed?
Secondary lymph tissues
B cell development requires what cells in the bone marrow?
Stromal
IgA exists on mucosal surfaces. T or F
T also exists in breast milk
Explain T independent antigens
T independent antigens don't require T cells for activation Two different antigen classes TI-1 (mitogens, e.g. polyclonal activators) At low concentrations they stimulate antigen specific B cells At high concentration they have the ability to activate B cells independent of antigen specificity LPS TI-2 (repetitive epitopes) antigens - B-1 cells respond Do not require T cells (athymic indiv can respond) Mostly against carbs on cells Predominately IgM, low affinity, no memory Without T cell signal there is poor switching
Explain TD and TI responses
TI antigens generate IgM responses prior to TD responses. TI antigen responses help to provide early defenses against infection, while TD responses are more specific, greater functional activities, and larger.
IgG is transported into the placenta. T or F
True it is maternal antibody
IgA and IgG are transported where by what?
across epithelial barriers y specific receptor proteins
What does IgM, IgG and IgA Ab protect?
blood and extracellular fluids
what happens if receptor editing fails?
clonal deletion results
BCR and what cooperate in B cell activation?
co-receptor
What do follicular dendritic cells capture?
immune complexes with anitgen on surface and present it to B cells
What do stromal cells do?
interact with developing B cells via surface adhesion molecules and ligands as well as produce growth factors
What does stem cell factor do?
interacts with Kit receptor on developing B cells promotes proliferation and development
What occurs in the secondary follicle?
isotype switching and somatic hypermutation
Can you form a B cell if you can't form IgM?
no
What are stromal cells?
nonlymphoid cells
B cells present specific antigen where?
to Th cells which deliver 2nd signals to B cells CD40L:CD40 and cytokines are 2nd signals for B cell activation
Explain the elimination of self-reactive B cells
Alter specificity or deletion binds to multivalent antigen found on cell surface of host cells Expression of surface IgM is reduced and RAG proteins remain high This allows continued rearrangement of light chain genes (receptor editing)
Explain the picture
B cell proliferation, differentiation, somatic hypermutation occurs in germinal centers
What is the most typical population discussed?
B2
What are the phases of B cell development?
Generation of B cells in bone marrow Elimination of self-reactive B cells in bone marrow Activation of B cells with foreign antigen in secondary lymphoid tissues Differentiation into antibody producing plasma cells and memory B cells in secondary lymphoid tissues.
Know this diagram
HC rarrangements followed by light chain If the first rearrangement of the V-DJ on first chromosome is un productive then second chromosome is used. If this rearrangement is unsuccessful we move to apoptosis
Explain the picture
T independent B cell activation TI-1 and TI-2 antigens LPS binding to TLR4 and Ig can trigger the B cell to produce antibody Bacteria can also be endocytosed and broken down. Bacterial DNA is sensed by TLR9 and if this occurs this will activate the B cell to produce antibody What's the importance of T indepdenent cell activation? Less time to generate Ab
Explain T dependent antigens
T dependent antigens requires T cells Requires T cells Memory Isotype switching Somatic hypermutation - fine tuning antibody specificity
What does B2 cells require for activation?
Th
What binds to C3d on bacterial surface?
CR2
Explain the image
HEV - high endothelial venules allow circulating lymphocytes to enter directly from blood circulation Naïve Th cells enter T cell zone and interact with dendritic cells. If there is bacteria there taken up by the dendritic cells they become activated and primed. At the same time B cells are migrating as well. If B cells recognize the bacteria they can provide the first signal. We now have a Th cell that is activated along with B cells that are activated and they come together to form conjugate pairs. Eventually they will migrate to form germinal centers. Once B cell is activated it has MHC II on it and it can present to Th cell
What does IL-7 do?
IL-7 produced by stromal cells stimulates growth and proliferation of late pro-B cells and pre-B cells
Explain the picture
If a B cell enters in and meets antigen it recognizes and interact with T cells that have also interacted with that same antigen they form a conjugate pair and migrate into the primary follicle and as they divide up and begin to expand they form germinal centers. The germinal centers is where a lot of expansion occurs. In the germinal centers there is a lot of follicular dendritic cells as well as some Th cells. As memory or plasma cells are formed they leave and circulate the body
What does TGF B preferentially stimulate?
IgA
What does IL4 preferentially stimulate?
IgE
How is a B cell inactivated?
It binds to soluble antigen Most IgM is not expressed on the suface but IgD is Binding of IgD does not activate the cell No second signal leads to anergy
Explain B1 subset.
Minority subset: B-1 Express CD5 and little to no IgD Arise from stem cells in prenatal period In adults, primary location in peritoneal and pleural cavities, and are self-renewing and dependent on IL-10. Prenatally, they lack of N-nucleotides, but postnatally can have N nucleotides Antibodies low affinity and binds to multiple antigens (polyspecificity). Good against polysaccharides Specific for polysaccharide and other carbohydrate antigens. Does not require Th cell help for activation
Explain circulation of B cells from blood into secondary lymphoid tissues
Must enter primary follicles (with follicular dendritic cells) to survive. If they don't enter they die Follicular Dendritic cells help B cell development Lots of competition to enter these follicles only a fraction make it If they can't make it to primary follicle they become anergic. Anergic B cells are trapped in T cell areas outside primary follicles and undergo apoptosis.
Explain the pic
Somatic hypermutation - Increased affinity of antibody to antigen. Step in affinity maturation Occurs in germinal centers Somatic hypermutation changes the BCR specificity If it increases the affinity for Ag those cells bind strongly and out compete cells who have low affinity for Ag
B cell development in bone marrow proceeds in stages. What are the stages?
Stem cell Early Pro-B cell (D-J rearrangement occurs in the heavy chain) Late Pro-B cell (V-D rearrangement) Large Pre-B cell (expresses Pre-B cell receptor) Small Pre-B cell (light chain rearrangement) Immature B cell (expresses surface IgM) Mature B cell (expresses surface IgM & IgD)
what does CR2 recognize?
complement component
What can B cells do after activation?
differentiate into plasma cells or memory B cells
what happens at the primary follicle?
primary follicle changes to a secondary follicle once the B cell gets there and it contains germinal centers
