development of B lymphocytes Flashcards
There are 6 phases of b cell development, which ones need an antigen
the last two; when it finds and attacks an antigen
CD 34 is
pleuripotent hemapoetic stem cell. can differentiate into either a b or a t cell
what cells affect b cell development
stromal cells
first change that you can see in B cell development
the rearrangement of the heavy chain gene locus; it starts with a d-j arrangement, then it goes to a v-dj rearrangement; this happens on both chromosomes and proves that it should live and progress on to the next stage
the pre-b cell stage has what kind of chains
it has a successful heavy chain attached to a surrogate light chain to physically support for the heavy chain expression on the cell surface
immature b cell stage has what kind of chains
it has a normal light chain (lambda or kappa) with a mu heavy chain; we replaced the surrogate light chain
during the pre b cell stage, what does rearrangement prevent
The b cell will not have multiple specificities per cell
light chain rearrangements are neat because
you can actually keep rearranging the light chains
after phase 1, we have what kind of B cells
B cells that could recognize anything… even your own tissues
what is negative selection
tests the B cells to see if it will react negatively against self cells; if it fails, it can rearrange the light chain; if it passes, it can leave the bone marrow
an immature B cell can also interact with what
serum albumin, a hormone… any soluble univalent self antigen; if this happens it undergoes anergy and then apoptosis
how do naive b cells get into lymph nodes
circulation through high endothelial venules and they attach there
how can a b cell leave a lymph node?
efferent lymphatic vessel
you have a b cell that is circulating but it is still immature. what cells can teach it what to do?
chemokines are secreted and the immature b cell can go near a folicular dendritic cell which will secrete b cell activating factor (BAFF)
after BAFF what is the B cell called
it is now a “mature” b cell
tumor of lymphoid progenitor
acute lymphoblastic leukemia
tumor of pre-bcell
pre b cell leukemia
activated/memory b cell tumor
chronic lumphocytic leukemia
germinal center b cell tumor
hodgkin’s lymphoma
mature memory b cell tumor
follicular center cell lymphoma
tumor of plasma cell
multiple myeloma
b cell usually requires what two signals
1) cross linking of two Ig from surface of Bcell delivers an intracellular signal
2) Th2 cell delivers second signal via CD40 on the Bcell
* *there is a third signal of cytokines that can signal it to do other things we will talk about later
when the Bcell cross links to antigens what are the two things that send the signal? what is the final result?
hetero dimer of Ig alpha and IG beta. this causes receptor associated kinases to stimulate downstream changes of gene expression
CR2 is a receptor for? Bcell function
it is the receptor for complement component C3d IT LOWERS THE ACTIVATION THRESHOLD TO ACTIVATE THE B CELL
4 options that happen after Bcell activation
proliferation - increase B cells with specific Ig
somatic hypermutation - nucleotide changes
isotype switching
development of memory Bcells and plasma cells
where does Bcell activation take place
germinal centers. the activated Bcells then move to the germinal centers to proliferate
mantle zone is?
naive non-activated Bcells
how do antigens get to the lymph node?
1) afferent lymphatics has whole Ag proteins, and macrophages take them into the primary follicle
2) follicular dentdritic cells eat it and present the Ag fragments
What are other cells that have the CR2
follicular dendritic cells, macrophages, Bcells
does the spleen have afferent lymphatics?
nope. they come in through the normal arteries.
the first ig that are secreted?
IgM
follicular dendritic cells fxn?
they don’t internalize Ags. they bind Ags while the B cells are undergoing somatic hypermutation. the ones that don’t have good mutations undergo apoptosis. the ones that have good compete for the Ag that the FDC is holding. the one that wins gets a survival signal
isotype switching… what are the two signals that are important
CD40L that is critical for Bcell to do isotype switching
i missed the second signal
IL-10 is involved in
induces differentiation into plasma cells
IL-4 is involved in
induces isotype switcing as well as the differentiation into memory B cells
overall, the T helper cell helps the B cells
decide whether they will turn into a plasma cell or a memory B cell.
hyper IgM syndrome mutation and outcome
mutation in CD40L so there is a lack of serum IgG and IgA with a compensatingly high level of serum IgM.
THEY WON’T HAVE GERMINAL CENTERS
TI-1 antigen
activates B cells without the help of Tcell. eg lipopolysaccharide
TI-2 antigen
repetitive epitopes that cause significant cross linking of Ig molecules on the surface of Bcells. if there is enough cross linking than there wiill be an activation of bcells.
eg. polysaccarides or proteins
TI-2 antigen poor response in
children that are less than 5 yrs old. so to protect from certain illnesses, this decreases the chance that you can get a good vaccine
TI-1 response can be in what people
athymic and infants
where can IgA be trasnported
across epithelial cells into mucosal secretions
where can IgG be transported
across endothelial cells or placenta
polymeric immunoglobulin receptor: specific?
no. it transports Igs that are polymorphic like IgA and IgM thats why you can find IgM in the mucous too
what does the polymeric immunoglobulin receptor bind?
the J Chain in a dimeric IgA that has a secretory component wrapped around the JChain segment
brambell receptors carry?
IgG across the endothelial cells into extracellular spacesl this explains why the IgG is most common in the extracellular matrix
At the time of birth, what Ab does the baby have
maternal igg, few igm and sparse iga
At six months old, what Ab doe the baby have
waning maternal igg, growing igg, maternal iga from milk, growing igm
antibody functions (3)
neutralization, opsonization, complement activation
4 examples of toxins that can be neutralized by antibodies
diphtheria, tetanus, cholera, staphaylococcus enterotoxin
Fc gamma receptors are expressed on
neutrophils, macrophages, bcells, follicular dendriic cells, nk cells
Fc gamma receptors enhance
phagocytosis of microorganisms by neutrophils and macrophages (opsonization)
Fc epsilon receptors are expressed on
mast cells and basophils
Fc epsilon receptor are important in
allergic reactions
Fc gamma R1 is expressed on
macrophages and neutrophils
fc gamma R1 is important in
facilitating the efficiency of phagocytosis
antibody dependent cell mediated cytotoxicity important in? what does this process need?
killing tumor cells via NK cells… except that NK cells have to have a way to know which cells to kill
