Lecture 12+13: B cells Flashcards by Riley Hrasky

what orchestrates the development of lymphocytes

stromal cells and cytokines

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what are lymphocytes (B cells, T cells and NK cells) derived from

Hematopoietic stem cells —> multipotent progenitor cells —> common lymphoid progenitor cells —-> lymphocytes

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antibody secreting plasma cells…AKA?

effector B cells

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adaptive humoral immunity mostly works against ?

extracellular microbes and their products

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what are the 2 classes of B cells

B-1 : Primarily mature in fetal liver, can self renew

Follicular B-2 cells: mature in the bone marrow

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what is the physical composition of B cells

4 peptide chains joined by disulfide bonds
- 2 identical heavy chains
- 2 identical light chains
– each w/ variable and constant regions

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what ligand does the transmembrane region of the B cell interact w/ for signaling

CD79 (Igα + Igβ)

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where does B cell development occur

bone marrow

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what cells direct the development of B cells in the bone marrow

Stromal cells

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the rearrangement of Ig genes starts w/ ?

rearrangement of the heavy chain

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early pro-B cell phase starts with what rearrangement

D-J rearrangement of heavy chain

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late Pro-B cell development phase continues with what rearrangement

V-DJ

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blocking what step in B cell development would prevent further development

large pre B cell

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what is allelic exclusion?

ensures B cell expresses only one receptor type

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why is it important that B cells don’t make more than one type of BCR

it would be detrimental to immune response

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what is X-linked agammaglobulinemia (XLA)

mutation in BTK
characterized by a lack of B cells and serum antibodies

BTK = important kinase in signal transduction from pre-B cell receptor
- BTK mutation cannot transmit the signal for proliferation and differentiation of pre-B cells
- results in apoptosis of the pre-B cell

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what does the Lare Pre-B cell step check for

checks for functional heavy chain
checks for compatibility w/ surrogate light chain

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rearrangements of the light chain starts with …..?

kappa
use of lamba is done to increase the odds of a successful rearrangement

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what does combinational diversity depend on

which V, D and J segments are used in the development of the BCR allele

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what is junctional diversity

during splicing, has to do with which specific nucleotides are added or deleted

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what type of surface receptor do immature B cells make

only IgM

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what occurs during receptor editing

a chance to save the self-reactive B cells
VJ rearrangements on the light chain can occur
light chain editing only (kappa followed by lambda)
new light chain and new IgM made
once again goes through negative selection process
heavy chain remains

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what occurs after immature B cells make it past negative selection

alternative RNA splicing of the primary RNA transcription occurs in B2 cells

this produces two different mRNAs
VDJ region combined w/ mu constant region
VDJ region combined w/ delta constant region

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what allows B2 cells to be able to synthesize both IgM and IgD

alternative RNA splicing

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what is the half life of mature B cells

100 days

what are the stages of B cell development?

Progenitor (Pro-B cell) Precursor (Pre-B cell) Immature B cell Mature, naive B cell

in what stage does the initial expression of CD19 and CD20 occur along with initiation of somatic recombination of the heavy chain

pro B cell

in what stage does the initiation of somatic recombination of the light chain occur

Pre-B cell

at what stage of B cell development does negative selection occur

immature B cell

what are the antigen-dependent phases of B cell development

B cell activation B cell differentiation

what are T-dependent antigens

protein antigens that lead to B cell activation w/ helper T cells

what are T-independent antigens

non-protein antigens that lead to B cell activation w/out helper T cells

where are B1 B cells located

in mucosal tissues and pleural/peritoneal cavities

what type of antigens do B2 B cells mostly respond to

T-dependent antigens

what type of antigens do B1 B cells mostly respond to

T-independent antigens

where do B cells circulate

between blood and lymphoid tissues to find antigens

what attracts follicular B cells to follicles

by B cell-specific chemokines produced by follicular dendritic cells (FDCs)

what happens if follicular B cells don't get activated in the follicles

they leave following the S1P gradient

how do antigens enter the secondary lymphoid organs from the lymph/blood

by crossing epithelial barriers or by being carried in via DC cells to interact w/ receptors on the follicular B cells

what is the first signal in B2 (follicular) cell activation

follicular B cells are initially activated upon antigen binding to the BCR for signal transduction, aggregation of receptors is needed to induce proliferation

how can aggregation of receptors occur

1. antigen binding and cross linking 2 or more BCRs 2. antigen cross-linking a BCR with the CR19/CD21 coreceptor

once follicular B2 cells are activated by the first signal where do they migrate to

the outer edge of the follicle into the T cell zone

B2 cells receive their second signal from what cells

Th cells and Th cell cytokines (CD40, CD40L) - IL4 induces the proliferation of Th cytokines

If B cells have a strong reaction to self during negative selection, what are the 4 possible fates

1. clonal deletion 2. receptor editing 3. anergy 4. immunologic ignorance

what is clonal deletion?

apoptosis of B cells that have a high affinity for self-antigen

what is receptor editing?

further genetic rearrangement to replace BCR with one that doesn't self-react

what is anergy?

a permanent state of unresponsiveness, eventually leads to death

what is immunological ignorance?

cells have an affinity for self-antigens but don't respond to them

what percent of immature B cells have some affinity for self

about 75% - they get sent for receptor editing

during receptor editing, V- J rearrangements occur on what chain

light chain

what stage of B cell development is characterized by the initial expression of CD19 & CD20

Pro-B cell

what stage of B cell development is characterized by the successful recombination and expression of the heavy chain as a Pre-BCR

Pre-B cell

what stage of B cell development is characterized by successful recombination and expression of a membrane-bound BCR complex

Immature B cell

what stage of B cell development does negative selection occur

Immature B cell

Non-protein antigens that lead to B cell activation without helper T cells

T-independent B1-B cells

where does the 2nd signal for B-cell activation come from

the interaction of the B cell with Th cell and Th cell cytokines

what occurs in the germinal center reaction

follicular B cells interact w/ follicular dendritic cells and follicular helper T cells - class switching from IgM ---> another isotope - affinity maturation = mutations increase binding affinity of antibodies to target

what is extrafollicular focus

A subset of the follicular B cells differentiate rapidly into antibody-producing plasma cells * Located outside of follicle = extrafollicular focus * Short-lived plasma cells producing low affinity IgM

after undergoing class switching and affinity maturation in the germinal center reaction, what happens to B cells

they differentiate into effector and memory cells

class switching is directed by?

Tfh interaction via CD40-CD40L

what immunoglobulin does IL-4 induce

IgE

what immunoglobulin does INF-y induce

IgG

what immunoglobulin does TGF-B induce

IgA

what is AID

an enzyme, Activation-induced cytidine deaminase functions by intentionally introducing mutations that must be repaired

can plasma cells present antigens

no b/c they cannot express MHC class II or co-stimulatory molecules they are entirely committed to making antibodies

activation of memory B cells is what kind of immune response

secondary

Lecture 12+13: B cells Flashcards

(66 cards)