B Cell Development Flashcards
what are we going to negatively select
anything against self will be eliminated
what is positive selection
promotion of some immature B cells to become mature b cells in secondary lymphoid tissue
B cell development as fetus happens where
fetal liver & bone marrow
once you’re adult where does b cell development happen
bone marrow
maturation and positive selection of b cell happen where
lymph node, spleen, peyer’s patches
what are central organs (primary)
bone marrow and thymus
hematopoietic stem cell is what CD
CD34
before you become B cell you make decision that you will be lymphocyte, and what is expressed
CD34 and CD10
CLP stands for what
common lymphoid progenitor
at immature B cell you have what
make u heavy chain and have IgM on surface
What is L chain on large pre-B cell
germline
what is L chain on immature B cell
VJ rearranged
what is the H chain on large pre-B cell
VDJ rearranged
What is H chain on immature B cell
VDJ rearranged
what makes pre-b cell a pre-b cell
surrogate light chain
what are needed at each stage of maturation
cytokines and cell-cell contacts
cell-cell interactions and cytokines regulate what
Regulates construction of the BCR
Ensures each B cell has one antigenic specificity
Clonal deletion of self-reactive B cells
Export of mature B cells
SCF stands for
stem cell factor
where is SCF expressed
stromal cells
SCF has receptor on surface of
b cell
what is SCF receptor on surface of b cell
Kit
what is the function of Kit-SCF
helps b cell survive (early pro-b cell stage)
Late pro-b cell has what signals that helps it continue
IL-7: IL-7R
what does IL-7R bind to
IL-7
where is IL-7R found
on b cell
nonproductive rearangemtn means
b cell will die
productive rearrangement means
b cell will live, did it right
If V-DJ rearrangment for late pro-B cell doesn’t work what appens
try V-DJ rearrangment on the other chromosome
if V-DJ rearrangemnt on the second chrom. you tried doesn’t work for Late pro-B cell what happens
death
if V-DJ rearrangement works for late pro-B cell what happens
signaled to survive and become pre-B cell
what has surrogate light chain
large pre-B cell
which of the following is expressed on surface of an immature B cell
IgM
what is expressed on mature B cell
IgD and IgM
surrogate light chain has what
VpreB and gamma 5
every single pre-b cell will have the same
surrogate light chain - it doesn’t vary b/w different light chains
light chain is always
different
if you have two different heavy chains what ahppens
theywil not bind the same pathogen. they will not be as specific
pts that do not have bruton’s tyrosine kinase
no B cells, no immunoglobulin (antibodies)
what does Btk stand for
Bruton’s tyrosine kinase
agammglobulinemia means
no antibodies in blood
X-linked agammaglobulinemia
no b cells and no immunoglobulin
They do not have bruton’s tyrosine kinase
what is the first checkpoint in b cell development
use surrogate to see if it can express pre-b cell receptor. if surrogate cannot bind then something is wrong and they induce apoptosis
selection of functional heavy chains
selection of functional heavy chain is which checkpoint
first
if the b cell surives checkpoint and has allelic exclusion what will it do
proliferate
after b cells proliferate what is re-expressed
RAG
what does RAG help do to pre-b cell
L chain rearrangement
for heavy chain it’s harder to get right b/c
you are deleting a bunch of space so if you deleted wrong then you don’t have anything to fix it (pg 19)
it’s easier to make light chain b/c
there are a lot of choices, can try tor lambda, kappa, etc. and if mom’s doesn’t work, then try dad’s. can do this for all of them
making L chain doesn’t work what happens
die
immature b cells will have exactlyt he same
h and light chain
what is the second checkpoint for b cell development
checking for functional light chain
some IgM will have antibody sight that is against
self
immature b cells are tested for what before they can leave bone marrow
for autoreactivity - to see if they are going to recognize self
what are three mechanisms for negative selection against tolerance to self
deletion
anergy
receptor editing
negative selection: deletion, describe
apoptotic death
negative selection: anergy, describe
paralysis of function
negative selection: receptor editing, describe
alteration of specificity
go back to DNA level and edit the V region of the light chain
when go back at DNA level for receptor editing what are the choices?
edit the V region of the light chain
why can’t you go back change heavy chain in DNA
you already deleted most stuff, so can’t fix it, it’s gone forever
define receptor editing
immature B cell binds multivalent self antigen, light chain rearranges for a chance to make BCR with new specificity
define clonal deletion
immature B cell binds multivalent self antigen leading to apoptosis
define clonal anergy
immature B cell binds soluble self antigen, becomes paralyzed
what is first that happens if you are in bone marrow and stromal cells expressing self antigen and you bind to it
this is bad - don’t want to bind to the antigen.
it is retained in bone marrow
how can you know b cell is immature
no IgD
if you do not react with self antigen when you are immature b cell what will happen
move to blood and express IgD and IgM and become mature
receptor editing, describe in detail what happens
go to DNA and edit light chain.
you can edit light chain and use mom or dad allele, still have a lot more choices to try until something works.
get rid of VJ chain we know is bad.
reactivate RAG. get new V and J together and make brand new VJ, hoping the new one will not be against self
VJ premade that was sent back by receptor editting is
reacting to self - so we don’t want that, want to get rid of it
during receptor editing rexpression of what
RAG1 & 2
once you have edited and chaged light chain from receptor editing, what happens
test on self and it doesn’t react, it can go into blood and mature
once you have dittied and changed light chain from receptor editing and it reacts to self again what happens
it will go back and get editted at DNA level and this keeps happening (to a point) until you get it right
when IgM of immature b cell binds to soluble univalent self antigen what happens
it is signaled to make IgD and to become unresponsive to antigens (anergic)
term for unresponsive b cell
anergic
once b cell is out of bone marrow and it is in blood where does it go
searches for lymph node or other secondary lymph organ
in order for b cell to fully develop it needs to go into
primary lymphoid follicle
HEV stands for
high endothelial venules
when b cell in HEV there will be what two chemokines
CCL21& CCL19
what do CCL21 and CCL 19 do
attract b cell into lymph node
follicular dendritic cells make what chemokine
CXCL13
CXCL13 does what
brings b cell into follicle
FDC stands for
follicular dendritic cells
follicular dendritic cell vs dendritic cell
very different, from different precurer, different function
follicular dendritic cell mainly found
b zone of lymph node
the reaction to get into the b zone of lymph node is
very compettiive
what happens if b cell doesn’t get into b zone of lymph node after it leaves bone marrow
it will die :(
the majority of b cell is what kind
B-2 Cells
describe B-2 Cells
what we have been talking about, the normal and what most people have
“Conventional B cells” derived from different progenitor cells than B-1 cells
Main players in adaptive humoral responses
Extensive N- and P- nucleotide
Extensive somatic hypermutation
B-1 cells are a subpopulation of
b cells
B-1 cells secrete
natural antibody - mostly IgM
majority of antigen B-1 cell responds to is
polysacharides (sugar!)
describe B-1 cells
Unique subpopulation of B cells
Extensively studied in mice but recently characterized in humans
Develop prior to birth
Secrete “natural antibody” (mostly IgM)
Little N-nucleotide addition or somatic hypermutation
Broadly antimicrobial - first line of humoral protection
are there memory for B-1 cells
no
B-1 cells are not derived from bone marrow they are
self-renewing
B-1 cells are first produced
fetus
b-2 are first produced
after birth
do b-1 cells require help from t cell
no
do b-2 cell require help from t-cell
yes
where is primary location of b-1 cell
peritoneal and pleural cavities
why don’t b-1 cells need help from t-cell
they don’t need help from t-cell b/c t-cell don’t see sugar, they only see linear peptides
explain heterogeneous vs. homogenous and allelic exclusion
you want the antibody, to have all the chains have the same specificity. that is why you only use mom or only use dad’s dna. if you don’t use allelic exclusion you would have heterogenous and each chain could want to bind to differnt things and it wouldn’t be efficient or effective.
if you use allelic exclusion, you will have only mom or only dad’s, so all the chains will want to bind to the same thing and will be effective.
where in the maturation process of b cell can you make mistakes and then have second and third chances to go back and fix
Rearrangement of the light-chain loci by pre-B cells is relatively efficient
which chain can you go back and fix and have “second chance” to make right
light chain
successive rearrangments are possible at:
Ig light chain loci
review and quiz on when proteins are active
pg 22
