B cell activation and antibody production (part II) Flashcards
B cells must etner ____ to become mature
spleen
precursor B cells – ________ –> immature B cell
VDJ recombination
membrane BCR vs Soluble BCR:
difference are in ____ region due to ____ ____
tail alternative splicing
____ and ____ are co-expressed on naive B cells through the mechanism of alternative splicing of the primary mRNA transcript of the Ig heavy chain locus
IgM and IgD
expression of AID (activation-induced [cytosine] deaminiase) requires ____ - ____interaction
CD40 - CD40L
CD40L is on T helper cells, so AID is only present in ____ responses (protein Ag only)
thymus (T-cell) dependent
in the GCs, B cells express activation induced deaminase (AID) which initiates somatic ____ and affinity ____
hypermutation
affinity
affinity maturation is observed only in Ab responses to ____ Ags
thymus-dependent (TD)
affinity maturation occurs within the ____ , where somatically mutated BCRs undergo selection on antigen retained on ____
GCs
FDCs (follicular dendritic cells)
Ag retained on FDCs are retained in the form of ____ complexes and involves the interaction of both ____ receptors and FcgammaRIIB with these immune complexes on FDCs
immune
complement
mechanism of affinity maturation:
- Dark Zone:
- AID creates ____ mutations in ____ regions (also called somatic hypermutation)
- light zone processes:
- changed BCR is exposed to Ag on ____
- increased affinity receptors receive stimulus to ____ , decreased affinity receptors do not
- process repeats so further ____ increases can occurs
- Dark Zone:
- point V
- light zone processes:
- FDC
- live
- affinity
B cell proliferation takes places in the ____ zone of the GC
dark
dark zone:
- cognate contact between TFH cell recognizing the Ag presented by B cells ____ B cell
- the T cell-derived cytokines stimulate proliferation and ____ of B cell clone
- the ____-____ interaction activates somatic hypermutation in proliferating B cells leading to diversification of BCR
- T cell-derived cytokines also stimulate ____ switch of Abs produced by activated B cell
- activates
- expansion
- CD40-CD40L
- class
affinity maturation results from repeated ____
mutations
light zone:
- B cell with mutated BCR performs ____ scanning and if BCR affinity is increased then B cell proceeds to start proliferation process over again
- if the mutated BCR has low affinity then this B cell undergoes ____
- FDC
- apoptosis
how increased affinity is determined:
- mutations correlate with increasing ____ of the Abs for the Ag that induced the response
- Ag recognition promotes expression of ____
- Ag recognition stimulates production of ____ inhibitor
- affinities
- anti-apoptotic Bcl-2
- Fas
stronger ____ → more stimulation → more Bcl-2 → stronger T cell interations (CD40-CD40L) → more Fas inhibitor
affinity
many tumors of B cells, B cell lymphomas develop from B cells in ____
its caused by chromsomal ____ of various oncogenes into Ig gene loci
the DNA breaks associated with somatic hypermutation and isotype switching facilitate incorporation of ____
GCs
translocations
oncogenes