Term
| Recombination/rearrangement in BCR |
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Definition
VJ(light) or VDJ(heavy) segments join
to form variable domain and
intervening DNA is lost |
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Term
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Definition
RAG1, RAG2, DNA enzymes
Recognize RSS(recognition signal sequence)
RSS: Heptamer(conserved) - 12 or 23
nucleotide spacer - nonamer(conserved)
12(one-turn RSS) pairs with 23(two-turn) |
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Term
Recombination / Variable generation
in BCR |
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Definition
RSS recognition by RAG; synapse formation
SS nick by RAG; ligation to form hairpin
Cleavage of hairpin, P-nucleotide addition.
TdT(Terminal deoxynucleotidyl
transferase) mediated N nucleotide
addition. Non template.
Trimming of free non DNA by exonucease
Free DNA ends aligned, polymerized and ligated. |
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Term
| P and N nucleotide addition |
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Definition
Removal or addition of nucleotides can
enhance antibody diversity but may
result in premature chain termination
Addition Happens on CDR3. |
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Term
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Definition
H-chain rearrangement done first, if
productive becomes pre-BCR if not try
allele 2.
Light Chain rearrangement has a total
of 4 alleles to try before destruction.
2k and 2 lambda
Once Good chain found -> block other allele. |
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Term
B-cell prior to antigen exposure
Pre-BCR
Immature B
Mature B |
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Definition
Pre-BCR: IgM H chain + surrogate L chain
Immature B: IgM
Mature: IgM + IgD. Co-expression is RNA
event.(alternative splicing) |
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Term
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Definition
Somatic Hyper mutation(SHM)
in germinal center of secondary follicle
Point mutations in variable domain of
exons (V(D)J) |
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Term
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Definition
Looping out and recombination by
Activation Induced cytidine
Deaminase(AID)
Switching increases diversity of Ig
function
T cell(CD40 & cytokines) dependent.
Translation of H chain constant region
and loss of intervening DNA |
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Term
| DNA vs RNA events in generation of diversity of BCR |
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Definition
RNA events are reversible and regulated
DNA are irreversible
Alternative splicing(RNA) leads to IgM
and IgD co-expression and membrane vs
secreted forms |
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Term
| B-cell and bone marrow interaction |
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Definition
Early Pro-b cell. SCF(BM) binds to
Kit(lymph cell) -> Il-7 release from BM
IL-7 signals H chain Rearrangement
When B-cell leaves BM it is immature.
Only expresses IgM |
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Term
| Pre-B cell receptor induction of Light chain rearrangement. |
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Definition
Surrogate light chain binds to H-chain.
Igα and Igβ(CD79a/b) required for
surface expression of BCR.
ITAMs are motifs with tyrosine residues
that cause a cascade leading to light
chain rearrangement
Bruton's tyrosine kinase deficiency ->
No signal transduction, no light chain
rearrangement. |
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Term
| Self-reactivity in B cells |
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Definition
Clonal Deletion: Immature B cell binds
MULTIVALENT self-antigen. Apoptosis or
receptor editing(light chain if
possible)
Clonal Anergy: Immature B cell binds
SOLUBLE self-antigen. Makes IgD and
becomes unresponsive to antigen(dies) |
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Term
| Where in lymph nodes are B and T cells activated |
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Definition
B cells activated via BCRs in cortex of lymph node.
Ig-alpha, Ig-beta RTKs send signals upon binding of antigen.
T cells activated by APC in paracortex |
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Term
| Activation of Src family kinases |
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Definition
ITAMS(CD79) are phosphorylated and Src
family kinases(Blk, Fyn) are activated
on antigen binding.
Increase in Ca++, PKC. ->>>
NF-kB, NFAT, AP-1(transcription factors)
New gene expressoin
CD45 removes inhibitory P on Src family
kinases |
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Term
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Definition
Antigen -> Src family kinases activated
ITAMs phosphorylated
Syk recruited, binds to IgB. -> PLC-y + GEFS.
PLC: PIP2 -> DAG + IP3 -> PKC and Ca++
-> NF-kB and NFAT
GEFS-> MAPK -> AP-1 |
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Term
| B cell Positive and negative co-receptors |
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Definition
Positive: CD19(pan b cell) or CD21
decreases threshold for immunogen
activation
Negative: FcyR has ITIM(inhibition
motif) Ag/Ab immune complexes bind BCR
and FcyR |
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Term
| Thymus Dependent Vs independent |
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Definition
Dependent:
Protein required.
APC activates Th cells
Th cells activate SMH.(Affinity)
Class switch or plasma cell via Th cell
Independent:
Polymeric antigens, don't bind T cells
B-1 -> IgM producing cells
Low affinity IgM. No class switch no
memory |
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Term
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Definition
Mitogens e.g. LPS binding TLR4
Production of Igm, rarely IgG/A
Lack of memory response
Non-specific polyclonal activation. |
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Term
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Definition
Multivalent or repetitive epitopes
(Polysaccharides)
Produce antigen specific antibodies
(may be presented on non-clasical MHC) |
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Term
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Definition
B-1(CD5): first made in fetus
Located in peritoneal and pleural
Self-renewing. IgM. No T help
No SMH, No memory
B-2: first made after birth
T cell Help for SMH, Memory, isotype
IgG dominant
In secondary lymph organs, replaced
from bone marrow |
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Term
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Definition
Signal 1 - BCR binds immunogen
Signal 2 - CD40(b-cell) binds CD40L(T)
Ag/MHC binding to TCR
CD4 from T-cell(co-receptor increases
avidity of MHCII/TCR.
signals B-cell to proliferate |
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Term
| B-cell development in germinal centers |
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Definition
Receives 1st T cell help:
Proceed to germinal center and
proliferate + SHM
Competition for antigen on
FDC(folicular dendritic cell)
affinity maturation
2nd T cell help -> memory B or plasma
Clonal selection, proliferation
Class switching |
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Term
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Definition
Occurs in centrocytes(B-cells) located in
dark zone of germinal center
AID(activation-induced cytidine
deaminase)
Deaminates cytidine residues
Repair leads to base changes. |
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Term
| Signal for memory or plasma |
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Definition
IL-10 -> Plasma cell
IL-4 -> Memory cells. IgG, A or E. |
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Term
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Definition
Production of plasma cells within primary
follicles expressing IgM days 4-7
Migrating to Germinal center for
affinity maturation, class switching,
plasma, or memory. Days 7-10
Plasma cells migrate to medulla and
produce antibody for 2-4 weeks |
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