26 - B cells: Overview of adaptive immunity, B cells & B cell activation (Signal 1&2) Flashcards by Fumeng Sun

Antigen presentation in

lymph node

How well did you know this?

Not at all

Perfectly

Activation of B - Signal 1

P:BCR (specific to an Ag)

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

IgM

Ab class
-serve as receptor on naïve B cells

BCR usually membrane bound is a IgM

How well did you know this?

Not at all

Perfectly

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)

How well did you know this?

Not at all

Perfectly

B cell activation concept:

Linked recognition

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

B cell activation leads to: … immunity

Humoral immunity(HMI)

How well did you know this?

Not at all

Perfectly

what are B cells

-Type of lymphocyte – from common lymphoid lineage
-Arise in bone marrow
-Leave to circulation & find Ag

How well did you know this?

Not at all

Perfectly

Key role in adaptive immunity of B cell

o Antigen specific
o B cells = clonotypic
o Progenitors of Ab-producing plasma cells & plasmablasts

How well did you know this?

Not at all

Perfectly

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.

How well did you know this?

Not at all

Perfectly

 Plasma cell

activated & differentiated B cells & main Ab-secreting cells

How well did you know this?

Not at all

Perfectly

 Plasmablasts

B cells in lymph node already showing features of plasma cells

In between: can secrete Ab & have membrane bound BCR

How well did you know this?

Not at all

Perfectly

BCR is… , but once secreted, it is know as

membrane bound

Ab (Ig)

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

B cell activation: Signal 1

Signal 1: BCR binds Ag

How well did you know this?

Not at all

Perfectly

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 1. 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 2. 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