Lecture 15 (Exam 2) Flashcards
Alternative processing of a primary RNA transcript results in the formation of _______ for the membrane or secreted form of the u heavy chain.
mRNA
Ag-dependent B cell activation results in an (INCREASING/DECREASING) fraction of the u protein produced as the secreted form.
Increasing
____, ____, and ____ refer to tail piece, transmembrane, and cytoplasmic segments, respectively.
TP
TM
CY
____, ____, ____, and ____ are four axons of the Cu gene.
Cu1
Cu2
Cu3
Cu4
This is the process that leads to increased affinity of Abs for a particular Ag.
Affinity maturation
Affinity maturation is observed ONLY in Ab responses to ____ Ags.
TD
T-FH cells and CD40:CD40L interactions are required for _______ _______ of Ig V genes to be initiated.
Somatic hypermutation
During the Germinal Center (GC) reaction, selection of B cells with high-affinity Ag receptors result in the production of _____ with high affinity for Ag.
Abs
Abs with an increased affinity (binding) to Ags more efficiently neutralize and eliminate _______.
Microbes
Affinity maturation occurs within the GC, where somatically mutated BCRs undergo selection on Ag retained on ______.
FDCs
Ag is retained in the form of ICs and involves the interaction of both complement receptors and _______ with these ICs on FDCs.
FcyRIIB
Affinity maturation is the process of “fine tuning” of B cell specificity that occurs through a repeated process of somatic hypermutation of ______ and subsequent clonal selection.
BCRs
Hypermutation can occur anywhere along the ______ region of the Ig genes.
VDJ
T/F. Both the heavy and light chain Ig genes can be hypermutated, a process of point mutation and repair in the genes encoding the BCR.
True
In the GCs, B cells express _____, which initiates somatic hypermutation of the Ag-binding site of BCRs. Generally, _____ induces cytosine to uracil deamination.
AID
AID
AID induces cytosine to uracil ________. This is a mismatch that can be repaired by base excision and mismatch repair mechanism, which recruits error-prone polymerases allowing any base to be incorporated.
Deamination
In proliferating B cells in the dark zone of GC, Ig V genes undergo point mutations at an extremely (LOW/HIGH) rate.
High
This rate is estimated to be 1 in 10(3) base pairs per cell division in V gene, which is about 1,000x higher than the spontaneous rate of mutation in other genes. For this reason, mutation in Ig V genes is also called…
Somatic hypermutation
The V(H) and V(L) genes of expressed heavy and light chains in each B cell contain a total of about _____ nucleotides. This implies that mutations will accumulate in expressed V regions at an average rate of almost one per ______ ______.
700
Cell division
Ig V gene mutations continue to occur in the progeny of individual B cells. As a result, any B cell clone can accumulate more and more mutations during its life in the _______ _______.
Germinal center
It is estimated that as a consequence of somatic mutations, the nucleotide sequences of IgG Abs derived from one clone of B cells can have as much as _____ percent gremlin sequence mutated. This usually translates to up to _____ aa substitutions.
5
10
The mutations are clustered in the V regions, mostly in the Ag-binding complementarity-determining regions. There are far more mutations in _____ than in _____ Abs.
IgG
IgM
Mutations correlate with increasing ________ of the Abs for the Ag that induced the response.
Affinities
Somatic mutation of V genes generates Abs with different affinities for _____.
Ag
Binding of the B cells to Ag displayed on _______ is necessary to rescue the B cells from apoptosis.
Follicular DCs (FDCs)
The B cells with the highest affinity for Ag thus have a selective advantage for survival as the amount of available Ag decreases during an immune response. This leads to an average (INCREASE/DECREASE) in the affinity of Abs for Ag as the humoral immune response progresses.
Increase
B cells may also present Ag to germinal center _____ cells, which promote B cell survival in a CD40-dependent manner.
T-FH (Follicular T helper)
The GC is B cells graveyard. In time, ____ is eliminated and less is available in the GC.
Ag
To be rescued from ________, B cells need to express Ag receptors with higher and higher affinity for the Ag. This selection process results in affinity maturation of the Ab response.
Apoptosis
B cells that are selected to survive in the _____ produce Ig with increased affinity for the Ag.
GC
T/F. Because somatic mutation also generates many B cells that do not express high-affinity receptors for Ag and cannot therefore be selected to survive, the germinal centers are sites of tremendous apoptosis.
True
B cells that have undergone somatic mutation migrate into the FDC-rich _______ zone of the germinal center.
Light
B cells with high-affinity receptors for the Ag are best able to bind the Ag when it is present at (LOW/HIGH) concentrations by follicular DCs, and these B cells survive preferentially because of several mechanisms.
Low
B cell Ag recognition by itself induces expression of anti-apoptotic proteins of the ______ family.
Bcl-2
High affinity B cells will preferentially endocytose and present the Ag for _____ cells in the GC with signal via ______ to promote the survival of the B cells.
T-FH
CD40L
Expression of endogenous inhibitors of _____ in high-affinity B cells may be activated when their BCRs recognize Ag and thus be protected from death, while low-affinity B cells are killed.
Fas
Many tumors of B cells, B cell _________, develop from B cells in germinal centers. It is caused by chromosomal translocations of various _______ into Ig gene loci.
Lymphomas
Oncogenes
In B cell lymphoma, the DNA breaks associated with somatic hypermutation and isotype switching facilitate incorporation of ________.
Oncogenes
Germinal centers may also contribute to the pathogenesis of _________.
Autoimmunity
Somatic mutation may produce a _________ B cell clone in the GC.
Self-reactive
In TD responses, some of the progeny of activated IgM- and IgD-expressing B cells undergo (HEAVY/LIGHT) chain isotype (class) switching and produce Abs with (HEAVY/LIGHT) chains of different classes, such as gamma, alpha, and epsilon.
Heavy
Heavy
Isotype switching primarily occurs in the germinal centers and is driven by ______ cells.
T-FH
Some isotype switching may occur in B cells in extrafollicular foci, driven by extrafollicular _____ cells.
Th
Class-switching occurs in response to changing the _______ regions of the _______ chains.
Constant
Heavy
Abs specificity which is determined by the _______ regions in the class-switched Abs remains unaltered.
Variable
The capacity of B cells to produce different ____ isotypes provides a remarkable plasticity in humoral immune responses.
Ab
Abs of various classes perform distinct effector functions and are involved in defense against different types of ________.
Pathogens
B cells activated by T-FH cell signals (______, cytokines) undergo switching to different Ig isotypes.
CD40L
Each class of Abs mediates distinct ________ functions.
Effector
Isotype switching in response to different types of microbes is regulated by cytokines produced by the ______ cells that are activated by these microbes.
T-FH
Intracellular pathogens activate helper T cells of the ______ subset, which produce the cytokine IFN-y and also likely induce IFN-y+T-FH cells to make increased amounts of IFN-y.
Th1
