Lectures 22 & 23 B and T Cell Development Flashcards
hematapoietic stem cells (HSC) divide and the progeny become ____ cells in the bone marrow
common lymphoid progenitor
in what stages of life does the transformation of hematapoietic stem cells to common lymphoid progenitor cells occur?
begins in fetal life and continues throughout life
common lymphoid progenitor cells that are destined to become B cells acquire ___ on their surface
B220 (CD45R)
once B cells have successfully rearranged their BCR (Ig_), where do the cells travel to?
IgM; travel to periphery where they mature in the spleen and then circulate as mature naive B cells between blood and lymph nodes
what recombination occurs in progenitor B cells?
DJH chain recombination and start of V-DJ-H recombination
what recombination occurs in pro-B cells?
V-DJ-H chain recombination
in what stage of B cell development is u H chain expressed as the pre-BCR?
precursor Pre-B cells
what type of recombination occurs in the precursor pre-B cells?
VJL chain recombination
in the pre-B stage, the cells undergo several rounds of ____
cell division
in what stage of B cell development are mIgM expressed?
immature B cells
in what stage of B cell development does negative selection start?
immature B cells
what type of negative selection are immature B cells capable of?
deletion & receptor editing
in B cell development, what is the effect of positive IL-7 signals on 1. survival & proliferation, 2. RAG 1/2 3. Vh-DJh rearrangement (HC allelic exclusion)?
- promotes survival & proliferation
- decrease RAG 1/2
- decrease VH-DJh rearrangement
what is the effect of negative IL-7 signals on:
- pre-BCR & IL-7 signals
- RAG 1/2
- light chain VLJL rearrangement
- proliferation
- decrease pre-BCR and IL-7 signals
- increase RAG 1/2
- increase light chain VLJL rearrangement
- decrease proliferation
pre-BCR made up of u heavy chain & surrogate light chains inhibits ___ rearrangement and induces ___ rearrangement
u; k
u & k in the pre-BCR inhibit rearrangement of ___allele and ___ rearrangement
K and lambda
in what part of the body does negative selection first occur?
bone marrow
t/f many B cells die in the bone marrow due to negative selection
t
what is central tolerance?
loss of B cells with self-reactive autoantibodies form the bone marrow
how does central tolerance of B cells occur?
clonal deletion of autoreactive B cells
what is clonal deletion?
induced apoptosis of IgM+ immature B cells with self-reactive BCR while still in the bone marrow
autoreactive B cells that are not caught by clonal deletion, can undergo ____ editing
light chain receptor editing
what segments get rearrange in light chain receptor editing?
the remaining V and J segments on the same chromosome
some autoreactive B cells that escape clonal deletion become ___ due to exposure to self-antigen or become unresponsive to antigen, these cells are called ___ and are short-lived
anergic; transitional T3
in light chain rearrangement, the first rearrangement btwn __ and __ regions is productive, but the combination of teh resultant light chain with Ab results in an ____ antibody
V3 and J3; autoimmune
in light chain receptor editing, the second rearrangement btwn __ and __ is productive and the combination with Ab heavy chain results in an _____ antibody
V2 and V4; nonautoimmune antibody
does the transition from immature to mature B cells occur outside the bone marrow?
yes
T1 B cells migrate to the ___ where a second round of ___ and further maturation occurs
spleen; negative selection
self reactive T1 cells are eliminated by ___
negative selection
the maturation of T1 B cells to T2 B cells is done by ____ selection
positive
T2 B cells mature to ___ cells, the largest pool of B cells
B-2
the transition of T2 B cells to B-2 cells is dependent on stimulation through ____
BAFF receptor
B-2 cells circulate for ~____ months
4.5
B-1, B-2, and marginal zone B cells all express __ and ___ immunoglobulins
IgD and IgM
during B cell development, the BCR signals through ____ and ___
Ig alpga and Ig beta
the BCR iga/igB have ____ motifs which can become phosphorylated
immunoreceptr tyrosine-based activation motifs (ITAM)
cross linking the BCR brings ___ into close proximity and they will phosphorylate the ITAMs
src family tyrosine kinases
phosphorylated ITAMS of BCR become docking sites for ____ and once it docks and becomes activated it causes multiple signalling events
syk kinase
what is the requirement for T-dependent B cells development?
contact with T cells through CD40 (using CD40L) to co-stimulate
are memory B cells made as a result of T-dependent or T-independent development?
T-depenent