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