Quiz 5 Part 3 Flashcards
immature B cell expresses functional ___
IgM
what regulates the expression of genes necessary for the recombination of heavy and light chain gene segments?
an extensive array of CYTOKINES and TRANSCRIPTION FACTORS
why is TIGHT REGULATION of key factors for B cell development needed?
since the same components are used in T cell receptor synthesis (ie: RAG complex)
when do immature B cells become mature
when they enter secondary lymphoid tissue
true or false…
the RAG complex (RAG1 and RAG2) is highly regulated
true
are D-J rearrangements all productive?
yes
VDJ joining as a ____ chance of being productive
1/3 (33.3% chance)
if V-DJ rearrangement is not productive at first, what happens next?
V-DJ is rearranged on second chromosome.
if fails there, then apoptosis
explain trial and error for the light chain rearrangement
rearrange K gene on first chromosome. if not productive, rearrange K gene on second chromosome.
if still not productive, rearrange lambda gene on first chromosome. if not productive, last chance is to rearrange lambda gene on 2nd chromosome.
if still not productive, apoptosis
BCRs (B cell receptors) that are able to bind human antigens (self antigens) are called….
self reactive or autoreactive B cells
if BCR binds self antigen….
further development is halted (this is like a 3rd checkpoint)
if the BCR DOESNT interact with self antigen…
alternative splicing mechanisms are activated and the delta chain is produced as well as the mu chain (IgM + IgD)
after alternative splicing mechanisms produce the delta and mu chains, what happens?
the BCR is released from the stromal environment (bone marrow) and enters circulation
explain the “bind self-antigen” checkpoint.
if the BCR’s do recognize self (in the bone marrow), they have another chance before they undergo cell death
they are kept in the bone marrow and undergo “receptor editing”
explain how receptor editing works
occurs in bone marrow.
SUCCESSIVE RECOMBINATION allows a B cell to produce a BCR that is self tolerant and will NOT bind self antigen anymore
if the BCR does not bind self antigen, a ______ survival signal is expressed
positive
list 2 things that happen when a BCR passes the “bind self antigen” checkpoint
-free to leave bone marrow
-begin expressing IgD
what does autoreactive BCR mean
A B cell receptor that binds self antigen
what exactly is being altered in the editing process of an autoreactive BCR
RAG is turned back on.
surface expression of IgM is reduced
the original light chain is excised (HEAVY CHAINS CANNOT BE ALTERED AT THIS STAGE) and a new rearrangement (new light chain) is produced.
if this new light chain assembles with the mu chain properly, development will proceed and the B cell will migrate to secondary lymphoid tissue to complete its development
If the BCR continues to bind self antigens, even after light chain rearrangement has been exhausted, what happens?
the B cell dies (called CLONAL DELETION)
The resulting B cell population that does not bind self is called…
self tolerant
what are “anergic” B cells?
they are in developmental arrest.
monovalent antigens do not signal cell death, but do not allow the progression of development either
they are inactivated and unresponsive. They still produce IgD due to having a “functional” BCR, but they cannot produce a survival signal and will die when they encounter an antigen
name the 3 fates of B cells in their development
-death by apoptosis
-survival through receptor editing
-rendered anergic
explain central tolerance and peripheral tolerance
central tolerance refers to the FIRST encounter that is possible for a BCR to come in contact with a self antigen (IN THE BONE MARROW)
however, sometimes self-antigen is NOT encountered in the bone marrow. it instead occurs after the B cell has entered circulation. this is called PERIPHERAL TOLERANCE
if a BCR binds self antigen while in circulation, what happens?
there is no receptor editing available at this point.
no longer expressing RAG complex proteins.
the cells will die (peripheral tolerance)
receptor editing is only available….
in the bone marrow
anergic B cell:
IgM levels are ____
IgD levels are ____
IgM levels are LOW
IgD levels are NORMAL
the anergic B cell enters peripheral circulation but does not last long. unresponsive to antigen and cannot produce survival signal
after leaving the bone marrow, immature B cells circulate between….
blood, lymph, and secondary lymphoid tissue
immature B cells are attracted to secondary lymphoid tissue by….
CHEMOKINES that are secreted by stromal cells in the LYMPH NODE CORTEX
chemokine = CCL21
What is the name of the receptor on B cells that recognizes CCL21 chemokine that is secreted by stromal cells in the lymph node cortex?
CCR7
Lymphocytes (B cells and T cells) are attracted to lymph organs by a mechanism similar to….
neutrophil recruitment (using different CAMS’s and chemokines)
_____cells in the lymph node also secrete ___ and ___ chemokines
dendritic cells
CCL21 and CCL19
B cells squeeze within secondary lymphoid tissue through…
a VENULE known as the high endothelial venule (HEV)
can B cells enter secondary lymphoid tissue through blood vessels?
yes
what chemokine attracts immature B cells to HEV?
CCL21 (secreted by stromal cells in the lymph node cortex)
what chemokine(s) attract B cells INTO the lymph node? in which specific part are the B cells entering?
CCL21 and CCL19, secreted by dendritic cells, attract B cells into the lymph node, specifically in the T cell area
what attracts B cells into the primary follicle?
the chemokine CXCL13 (secreted by FOLLICULAR DENDRITIC CELLS FDC’s)
what exactly drives the maturation of immature B cells?
contact with follicular dendritic cells promotes the survival and differentiation of immature B cells into mature B cells
LYMPHOTOXIN and BAFF promote the survival of FDC’s and B cells
what is the specific role of CCL19 and what is it secreted by?
to open the gap junctions of HEV (high endothelial venule) to attract B cells into the lymph node.
secreted by dendritic cells in the lymph node
what expresses a BAFF receptor?
what expresses an LT receptor? (lymphtoxin)
B cells have a BAFF receptor
FDC’s have a lymphotoxin receptor
if antigen is not encountered within secondary lymphoid tissue (lymph node) what happens to the B cells?
the B cell detaches from the FDC (follicular dendritic cell) and exits the lymph node as a mature B cell through the efferent lymphatic vessel.
in order to exit, Naive B Cells (those that did not encounter antigen) must compete for space with ____ that are already occupying the lymph node
mature B cells
if the immature B cells DO encounter an antigen in the secondary lymphoid tissue, what happens?
the B cells are detained in the T cell area.
CD4+ (helper T cells) known as FOLLICULAR HELPER CELLS activate B cells to proliferate and differentiate
helper T cells (CD4+) known as follicular helper cells (Tfh) activate B cells to proliferate and differentiate if they encounter an antigen within the lymph node.
explain the 2 possible paths of these B cells
some of the B cells immediately differentiate into plasma cells and secrete IgM
some B cells migrate BACK into the primary follicle (which is now SECONDARY FOLLICLE with a germinal center). here, the activated B cells undergo somatic hypermutation and isotype switching (ex: IgM–>IgG)
affinity maturation and isotype switching — cells mature into plasma cells
What is Hodgkin’s disease?
a B cell tumor arising from a single B cell in the germinal center
germinal centers are located where?
in the secondary lymphoid follicle
How do memory B cells become memory B cells
as the immune response proceeds, some of the germinal center cells develop into quiescent, resting B cells (dormant). these are memory B cells
Explain the purpose of memory B cells
memory B cells express HIGH AFFINITY, isotype-switched B cell receptors.
they are permanent members of the B cell repertoire and persist throughout life.
they undergo RAPID activation and differentiation into antibody-secreting plasma cells
do memory B cells require follicle-dependent stimulation?
only intermittent stimulation
Memory B cells are part of the ___ immune response
secondary
name 3 places where memory B cells reside
-medullary cortex of lymph node
-red pulp of spleen
-lamina propria of MALTs and in the bone marrow
in an immature B cell that has undergone alternative splicing, IgM is __ and IgD is ___
IgM is high and IgD is low
in a mature naive B cell, IgM is ____ and IgD is _____
IgM is low and IgD is high
what is the purpose of memory cells
to prepare for future infection
