2.3 - B Cell Development Flashcards
B cells develop in the
Bone marrow
Both T and B cells are derived from the ___ which expresses ___ marker
Pluripotent hematopoietic stem cell
CD34
What is the specific marker expressed in B cells?
CD19
What’s the specific marker for T cells?
CD3
Does B cell rearrangement happen in the heavy or light chain first?
Heavy chain
Heavy chain is designated by what greek letter
mu (µ)
___ expresses IgM on its surface with either kappa or lambda light chain
Immature B cell
What cells play an important role in B cell maturation?
BM stromal cells
BM stromal cells produce __ signal
IL-7
A critical cytokine in the development of B cells is ___. It is the ___ force for B cell to go from early B cell to immature B cell
IL-7
What receptor do B cells express so a cytokine can bind to it and drive it to maturation?
IL-7 receptor
Describe heavy chain rearrangement
- Occurs on chromosomes 1 and 2
- Occurs on chromosome 1 first and if successful it moves on to light chain rearrangement
- If not successful, it moves on to chromosome 2, and if that’s successful it moves on to light chain rearrangement
- If neither successful, cell undergoes apoptosis
Light chains contain a ___ chain during the early part of the development process
Surrogate light chain
What are the signaling markers for B cells that send signals to the cell interior when the B cell receptor binds an antigen?
Igbeta and Igalpha
The surrogate light chain is expressed in the
cytoplasm
There is rearrangement in light chains, this does/does not occur b/c of allelic exclusion
does
When 1 chromosome rearranges, the other one does/does not shut down
Does
allelic exclusion gives ___ B cells receptors w/ ___ avidity binding
Homogenous
High
No allelic exclusion gives ___ B-cell receptors w/ ___ avidity binding
Heterogenous
Low
Describe light chain rearrangement
- Rearrangement of kappa gene on first
chromosome → cell expresses mu and kappa - If that doesn’t work, rearrangement of kappa
gene on second chromosome → cell expresses
mu and kappa - If that doesn’t work, rearrangement of lamba gene on first chromosome → cell expresses mu and lambda
- If that doesn’t work, rearrangement of lambda on second chromosome → cell expresses mu and lambda
- If that doesn’t work, apoptosis
Are there usually more kappa or lambda light chains? what’s the ration?
Kappa
2:1
Checkpoints occur after which rearrangements? What happens if the chains don’t rearrange?
Occurs after heavy and light chain rearrangement
Apoptosis
IL-7 receptor function
Growth factor receptor
Igalpha and Igbeta function
Signal transduction
CD19 function
signal transduction
Pax-5 function
Transcription factor
Describe B1 lineage
- short lived plasma cell
- 1st B cell produce in BM before birth
- has a restricted V region
- Can self renew after birth
- Little memory development
Where can you find B1 lineage?
Medullary cords in LN
Red pulp spleen
secondary lymphoid organs
What isotype does the B1 lineage secrete?
IgM
Describe B2 lineage
- Short and long lived
- produced after birth
- In the bone marrow
- Diverse V region
- Replaced from bone marrow
- Has memory development
Where can you find the B2 lineage?
BM
What isotypes does the B2 lineage secrete?
All 5
B1 is a ___ B cell
CD5+
B cells that recognize self undergo ___ selection
Negative
If a B cell reacts w/ self antigen does it stay/leave the bone marrow. What then happens?
Stays
It goes through self editing in the light chain, NOT in the heavy chain, to produce a non self reactive light chain
- it undergoes rearrangement
If a B cell doesn’t react w/ self antigen, the B cell moves to the ___ and expresses what lymphoids?
Blood to go to secondary lymphoid organs
IgD and IgM
If there’s unsuccessful editing for the light chain, what happens?
apoptosis
What is central tolerance?
Soluble univalent self antigens interact w/ igM on the surface of B cells and the cell becomes unresponsive or anergic
- When there’s neg selection
What is peripheral tolerance?
- Develops after B cell leaves BM and then encounters self antigen
- The self reacting B cells die or become anergic
Steps for B cell entering lymph node and leaving
- Enters through HEV
- goes to primary lymphoid follicle
- Leave via efferent lymphatic to go to blood
When B cells go to primary follicle, what then happens?
it interacts with follicular dendritic cells which aids in the maturation of the immature B cell into a mature, naive B cell
Describe follicular dendritic cells
- doesn’t have hematopoetic origin
- doesn’t process antigen, just holds it on its surface
- not a dendritic cell
- displays dendritic extensions
What happens in positive selection?
B cells interact w/ FDC or they die
Where can B cells encounter an antigen in the lymph node?
In the B cell region or germinal center
When B cells differentiate into plasma cells, they migrate to
Medullary cord in the lymph node or the bone marrow
B cells make antibodies which deal w/ microorganisms outside/inside cell. B cells undergo ___ immunity
Outside
Humoral
The co-receptor of B cells
CD19
Describe T-dependent responses
- Requires T cell help for B cell to become activated
- Involves B2 lineage
- involves the TH2 and TfH subset
- required for the majority of antibody responses
Describe T-independent responses
- B cell can interact w/ antigen and become activated w/o T cell help
- involves B1 lineage
B cell activation steps to turn into plasma cell
- IgM bind to antibody on surface of B cell
- Microorg is processed and presented on MHC II
- antigen’s recognized by helper T cells
- helper T cell’s activated and releases cytokines
- B cell turns into plasma cell
First signal in B cell activation
B cell interacting with its specific antigen through the B cell receptor
Second signal in B cell activation
Interaction of the TCR w/ the MHC class II molecule on the surface of the B cell which contains the process antigen
What’s an important component of the second signal in B cell activation?
Interaction of CD40 on the B cell surface w/ its ligand CD40 on the T cell
