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
