26 - B cells: Overview of adaptive immunity, B cells & B cell activation (Signal 1&2) Flashcards
Antigen presentation in
lymph node
Activation of B - Signal 1
P:BCR (specific to an Ag)
Activation of B cells via TFH - Signal 2
TCR(of TFH):pMHC II (on B cells)
B cell presdent peptides on MHC II
CD40L(from TFH):CD40
IgM
Ab class
-serve as receptor on naïve B cells
BCR usually membrane bound is a IgM
Additional signal
cytokine (IL-21- important for proliferation of B cells)
tell B cells what Ab to produce
-type 1 (INFy)
-type 2 (IL-4)
-OR type 3 (IL-17)
B cell activation concept:
Linked recognition
when a B cell is activated, it’s differentiated, it’s proliferated,
it’s going to
produce Abs that promotoe:
o Pathiogen neutralization
-Bind to pathogen (virus-need to replicate) - so it cant bind ot other things
o Opsonization
-Phagocytosis
o Complement activation
-C1q bind to Ab bound to pathogen – lead to complement pathway
B cell activation leads to: … immunity
Humoral immunity(HMI)
what are B cells
-Type of lymphocyte – from common lymphoid lineage
-Arise in bone marrow
-Leave to circulation & find Ag
Key role in adaptive immunity of B cell
o Antigen specific
o B cells = clonotypic
o Progenitors of Ab-producing plasma cells & plasmablasts
what is clonotypic?
B cells, just like T cells, each cell has a specific TCR or BCR specific for a particular antigen.
Once it finds its match, we need clones of that particular B cell to then clear the infection.
- clonal selection and expansion.
Plasma cell
activated & differentiated B cells & main Ab-secreting cells
Plasmablasts
B cells in lymph node already showing features of plasma cells
In between: can secrete Ab & have membrane bound BCR
BCR is… , but once secreted, it is know as
membrane bound
Ab (Ig)
Clonal selection & expansion (Steps)
Process of clonal selection
-Clonal deletion happens if autoreactive
-Activated B cells undergo proliferation & differentiation
-Once it has found its Ag match clonally selected & expanded
-Outcome = plasma cell that secrete Ab
- Gene arrangement of BCR
-diversity - in Bone marrow, Clonal deletion happens if autoreactive
- go in circulation
- find Ag match: clonally selected & expanded
- plasma cell that secrete Ab
B cell activation: Signal 1
Signal 1: BCR binds Ag
B cell activation:
B cell enter lymph node
- Naïve B cells circulating in periphery pass through lymph nodes & spleen regularly
- Enter lymph node through HEV
-If B cells doesn’t encvounter Ag, leaves via efferent lymphatics
-If it doesn’t encounter Ag after a few months, dies via apotosis - If B cell encounters Ag, provides survival signal (SIGNAL 1)
– for T cell is signal 2
B cell activation: Signal 1
difference between B cell signal 1 & T cell signal
the survivial signal 1 for B cell is the signal 2 for T cell
B cells look for Ag, NOT p:MHC (T cell)
B cell activation: Antigens in lymph node
- Ag from pathogens arrive in lymph node via afferent lymphatics
- Ab can be covalently linked to complement components - opsonized
- Ag can be then retained in lymph node by SCS macrophages & follicular DC (Resident DC)
How are Antigens retained in lymph node??? step by step
- Opsonized Ag enter lymph node
- Ag are opsonized if linked with compliment component - In lymph node, SCS macrophage – subcapsular sinus macrophage
-Express complement receptor on their surface
-Can bind complement on opsonized Ag –> retain the Ag in lymph node - SCS macrophage retain Ag on their surface in lymph node
-These macrophages have low endocytic & degradative activity - Some Ag = free floating in lymph node
-Most are retained by SCS - B cells that enter lymph node can encounter this Ag
- Ag can also be transported by SCS macrophages onto surface of follicular DC
- important for later stages in B cell differentiation
BCR binds specifically bind to… on Ag
an epitope on Ag
Ag binding to BCR – trigger ….
trigger signaling
- BCR binds Ag
-sometimes the pathigen is coated with complement proteins - B cells also express: co-receptor, complement receptors
-CD19 & CD20 - Binds complement component bound to pathogen
- BCR associated with signaling subunits Igα & Igβ
-They have ITAM that become phosphorylated
what is not necessry for signal 1, and why?
B cell binding to complement protein bound to pathogen
-because there there are some antigens that are free floating. They will still be able to give signal 1 to the B cells
BUT, it Can enhance signaling & activation
Signaling can also happen…
via co-receptor complex (Complement receptor)
-if there is a complement receptor binding to a complement protein.
Signaling outcomes
Phosphorylation of ITAM motifs on Igα & Igβ
Multiple signaling pathways activated
Main outcomes of signal 1:
Transcription factors are activated
-gene transcription – B cell survival
(B cell proliferation & differentiation)
Cytoskeleton reorganization–endocytosis of BCR & AG
Once signaling begins,
BCR-Ag complexes = internalized (endocytosed)
Internalized Ag = processed & presented on MHC
pMHC can then interact with TCR on T cell for TFH
What describes the pathway used to process Ag and the MHC class used to present on B cells?
Exogenous pathway (B cell mediate entry, not the antigens mediating its own entry)
MHC class II
Signal 2:
interaction with T cell
signal 2, different types of antigens
Thymus dependent Ag (TD antigens) more likely to happen
Thymus-independent Ag (TI antigens) less likely to happen
Thymus dependent Ag (TD antigens)
Signal 2 is provided by activated CD4+ TFH cell
T cell dependent
Specific Ag & provide memory
Thymus-independent Ag (TI antigens)
Doesn’t require T cell
Signal 2 provided by TLR signaling
-only subset of B cells have this TLRs (combine to
-Such Ag = typically highly repetitive molecules (LPS)
Only for some B cells:
B-1 & marginal zone B cells
- found in spleen
-Less diversity & give rise to primarily IgM antibodies
TFH cells provide help to B cell
-Signal 2, what are the different signals we see? (3) and the results
Signal from pMHCII bound to TCR & co-receptor on TFH cell
Signal from CD40 on B cell bound to CD40L on TFH cell
Result =signalling & activation of TF
-Lead to activation, proliferation, differentiation –> antibody secretion
Other signals = cytokines
-Tell B cell which Ab to secrete
Linked recognition: Difference between T cell & B cell
BCR can see Ag in its natural form
TCR can only see small pieces from Ag bound to molecules of MHC on surface of APC (antigen presenting cells)
Linked recognition definition
Rule that for a TFH cell to be able to activate B cell, the epitopes recognized by B cell & TFH cell must be derived from same Ag
(same source)
TFH recognize fragment of same Ag as recognized by B cell
-Peptide recognized by TFH cell = likely to differ from protein epitope recognized by BCR, but come from same Ag
–Peptide = processed & presented to TFH TCR vs. natural form for B cells BCR
T cell recognizes
epitope presented by MHC on DC
could be peptide from a protein inside viral particle
- Specific T cells activated by Ag that may reside within the viral particle
B cell recognizes
epitope
Native structure of a protein on viral surface
- B cell that recognizes a surface epitope of virus can process & present other Ag epitopes
which are characteristics of B cells?
A: survival signal for B cells = mainly provided by TFH
B: signal 2 mianly provided by TFH through interactions with their TCR & CD40L
C: can endocytose p:BCR
D: can bind Ag that are bound to SCSM
E: their CD19binds to complement proteins bound to Ag, enhancing B cell survival signal
B, C, D, E
summary:
Intro to B cells (what is B cell) -3
o Ag specific
o Clonotypic
o Ab-producing plasma cells & plasmablasts
summary:
Signal 1: BCR bind Ag in lymph node
o Ag must enter lymph node
o Roles of SCS macrophages
o Signaling:
-Transcription
-Survival signal
-Endocytosis
–Ag processed & presented on MHC
summary:
Signal 2: B cell interacts with TFH cell
o B cell present Ag on MHC II
o Interacts with TCR on TFH cell
o CD40 on B cell binds CD40L on TFH cell
summary:
Linked recognition
Same Ag (different epitope) presented to T cell by DC & by B cell
But via different route
