Flashcards in MCM 2-11 B-Cell Immunity Deck (17)
steps of B cell development
1. stem cell develops into early pro-b cell
2. rearrange D and J loci of its heavy chain on both chromosomes
3. successful - becomes late pro-b cell and begins rearranging its DJ locus with V loci on first chromosome, unsuccessful, will begin rearranging other chromosome
4, successful - will produce a pre-BCR (with productive heavy and surrogate light) which will signal its success and allow it to become a large pre-B cell
5. large pre-B cell will rearrange the loci of its light chain genes on both chromosomes (one kappa gene and one lambda gene on each chromsome
6. becomes small pre-b cell, will start by rearranging loci of kappa gene on first, then move to second kappa if fails
7. if either produces productive light chain, will become immature B expressing mu (heavy) and kappa
8. if both fail, will go on to lambda, if either successful, expresses mu and lambda as immature B cell
9. result of the light chain rearrangements is a cell wiht a functional IgM (B cell receptor)
having multiple genes to rearrange developing B cells more chances to produce a productive IgM and avoid apoptosis
what eliminates self reactive B-cells?
central tolerance - if immature B reacts with membrane bound self-antigen it will be retained in bone marrow and eventually die. If it does not react with membrane bound self antigen, it will leave bone marrow.
peripheral tolerance - if an immature b cell outside of bone marrow interacts with free floating soluble self antigen, it will be signaled to produce IgD and no functional IgM and to become unresponsive to antigen.
-This inactive state is referred to as anergy. Anergic B cells enter the peripheral circulation and die soon afterwards.
describe how receptor editing can rescue self-reactive b cells
if a membrane bound self antigen in bone marrow ligates an immature B-cells IgM, it will undergo receptor editing.
it will rearrange light chain genes to produce new IgM with a different specificity. If self-reactive, will continue until it creates an IgM that is not self reactive or dies.
If and when it creates a non self-reactive IgM, the b-cell will leave the bone marrow
Describe B cell receptor and co-receptor
Receptor - composed of a mu heavy chain and either a kappa or lambda light chain
Co-receptor - assists in antigen recognition and signaling. They are made up of CD19, a complement receptor CR2, and CD81
describe the process involving the final maturation of B-cells
Naiive b-cells (having passed both central and peripheral tolerance tests aka negative selection) are attracted to the lymph node and primary follicle through a series of chemokines.
Naiive B-cells will search for a specific antigen displaced on the FDC within the primary follicle "B-Cell Area". Naiive T-cells search for specific antigen presented by classical dendrites in the T-cell area
Antigen activated T-cells proliferate and differentiate
Antigen activated B-cells move to boundary region and present antigen on their MHCII molecules to the CD4 T-cells forming cognate pairs.
The helper T-cell conjugates with the B-cell, begins expressed CD40 ligand (critical for activation of other cells) and synthesized cytokines (to let the B-cells know to switch properly and give the correct type of response to that antigen). The T-cell reorients cytoskeleton towards the b-cell, secretes cytokines which drives B-cell diversification/class switching.
antigen-activated b-cells will either move to medullary cords (primarily) or the primary follicle to generate the germinal center (area that promotes receptor class switching and somatic hypermutation)
in germinal center, the b cells that will bind antigen, interact with T-cells, survive, and divide will be ones with highest affinity BCR's.
B cells with lower affinity BCRs will be outcompeted and die.
this is how high affinity b-cells are selected for. The end results are high-affinity b-cells that have differentiated into memory or plasma cells.
describe t-cell independent b-cell stimulation by antigen
highly cross-linking, repetitive antigens can stimulate B-cells independent of T-Cell assistance. After an antigen cross links B-cell receptors, a signalling cascade is induced that leads to changes in gene expression in molecules.
describe the properties of memory B cell
relatively rare, resting, long-lived cells.
typically class switched cells that produce high-affinity antibodies following secondary infection.
they express IgG or IgA
describe B1 cells
B1 - more primitive, produced early in fetus, not much TDT, there for first line of defense, produce natural antibodies even though no pathogen has been seen. Self renew, don't need to come from bone marrow, T-cell independant, no memory
almost all IgM
Describe B2 cells
derived after birth, more variability, replaced from bone marrow, Mostly IgG. high somatic hypermutation, can develope into memory cells
what are the options for dealing with a faulty b cell?
kill the cell, change its receptor, or render it anargic with the soluble self-antigens it binds to and then dies
______ brings antigen and b-cells together
describe how Tcells help drive B cell proliferation and differentiation
antigen recognition by T-cell induces expression of effector molecules by T-cell, which act on and activate the B-cell
the b-cell proliferates, and differntiates into resting memory cells and antibody secreting plasma cells
describe how naiive B cells and T cells find each other
naive b cells search for specific antigen displayed by follicular dendritic cell in the b-cell area; naive t-cells search for specific antigen presented by classical dendritic cells in the T-cell area (Surface)
antigen activated t-cells proliferate and differentiate, antigen activated b-cells move to boundary region
antigen-activated b cells present antigen to effector (Tfh) cells, forming cognate interactions and cognate pairs
what occurs in the germinal center?
final maturation of high affinity B-cells occurs. they interact with t-cells and FCD's
describe plasma cells
sit in bone marrow, antibody factories
lose surface Ig, no longer looking for antigen. don't need to grow or switch or interact iwth T-cells
what is the output of the germinal center?
somatic hypermutation and survival of the fittest generates high-affinity memory and plasma cells