BIOL 0530 Important Terms 2

B cell receptor

BCR stands for

immunoglobulins

soluble BCRs are known as antibodies or

antibody production, cytokine production, antigen presentation

three functions of B cells

bone marrow

B cell development happens here

periphery

any place/tissue that is not the bone marrow

Cell surface markers (CD markers), Transcription factor expression, Immunoglobulin rearrangements

these three things define the stages of hematopoiesis; allow us to know how far along a blood cell is in development

common lymphoid precursor

CLP; can differentiate into B cells, T cells, dendritic cells, and NK cells

secondary lymphoid tissue

when a B cell is mature, it can move from the bone marrow to here

stromal cells

these in the bone marrow provide support and growth factors to instruct B cells how and when to mature

pro, pre, immature

B cell development is as follows:

_____ B cell → ____ B cell → ______ B cell → can leave bone marrow

2

an antibody is made of heavy and light chains. how many of each?

disulfide

light chains of an antibody are held together by intra/interchain ________ covalent bonds

kappa, lambda

two types of light chains

epitope

Antigen binds to antibody at this location (on the antigen)

antigen binding site

the paratope on an antibody is also known as the

Susumu Tonegawa

Identified the genetic mechanism that produces antibody diversity; Somatic V(D)J recombination theory

germ line theory

an antibody generation theory that states that each antibody encoded by a gene in genome; incorrect - too many antibodies compared to genome)

somatic V(D)J recombination theory

an antibody generation theory that B cell have a limited germ line antibody genes. Mutational process in B cells used to alter genes within a cell

BamHI

enzyme that cut DNA at specific places in the Tonegawa experiment

somatic recombination

during development, the B cell shuffles its gene segments to produce millions of varieties of antibodies; this concept is known as

1

how many BCR types per one cell?

D

out of “VDJ”, which component do light chains lack?

D and J

out of “VDJ”, which two components add together first on a heavy chain?

recombination signal sequences (RSSs)

DNA recombination in antibodies is directed by these which help RAG 1 and 2 enzymes find V, D, and J segments of antibody

Heptamer, Spacer, Nonamer

the RSS contains these three parts

RAG 1/2 recombinase

during DNA recombination in B cells, gene segments are joined by these which recognize RSSs

recombination activating gene (RAG)

in DNA recombination in B cells, the enzyme (includes 1 and 2) that catalyzes DNA cutting is called

excision circle

DNA that is cut out during DNA recombination is called this; also called a signal joint

artemis

this enzyme opens DNA hairpin

junctional diversity

potential for diversity at joining sites on the heavy chain is known as

combinatorial, junctional

two types/sources of antibody diversity in B cells

false (heavy chain first)

(true/false) light chain recombination precedes heavy chain recombination

Ku70/80

during DNA recombination, this is recruited to ds break and serve as tool belt for other enzymes to assemble

P nucleotides

these are added to complement overhangs during DNA recombination

ligase

in the light chain, during DNA recombination, the enzyme attaches DNA segments together

exonucleases

in the heavy chain during DNA recombination, these may trim overhangs, possibly resulting in more antibody diversity

TdT

in the heavy chain, during DNA recombination, this adds non templated nucleotides after exonuclease trimming (N Nucleotide addition)

Terminal deoxynucleotide transferase

TdT stands for

CXCL12

Ligand in high concentration that keeps B cell in the bone marrow

CXCL4

B cells have a receptor ______ that binds to CXCL12

downregulates

When B cell is mature, it _________ (upregulates/downregulates) CXCL4 so it can leave the bone marrow

IL-7

B cell stromal factor; Once it binds to its receptor on B cell, starts V(D)J recombination

Central tolerance

Occurs when B cell is immature and self reactive; B cell must be removed; In the bone marrow

negative

central tolerance is an example of positive or negative selection?

self

in order to move on from central tolerance, B cells must not bind to tightly to ______ antigen in the primary lymphoid organ

autoreactive

B cells that bind self antigen are known as

receptor editing, apoptosis, anergy

three outcomes if BCR binds too tightly to self antigen during central tolerance

receptor editing

if a BCR binds too tightly to self antigen, it may undergo this process where its genes are rearranged using Rag 1 and rag 2 in light chain

rag 1 and 2

which two enzymes assist in receptor editing of B cells by dimerizing and creating a DNA loop?

anergy

permanent unresponsiveness; The cell doesn’t die, just becomes quiet

Newmazee

this experimenter hypothesized that something must be stopping autoreactive B cells from out of the bone marrow, and that that “something” was editing autoreactive B cells into non-autoreactive B cells to allow them to move through the bone marrow into the periphery

light chains

Receptor editing of potentially autoreactive receptors occurs in light chains or heavy chains?

More BCR expressed on the surface, More IgD and less IgM, Baff receptor expression

three changes that occur from t1 → t2 B cell

constant

in order to transition from T1 → T2 B cell and consequently start expressing more IgD and less IgM, which part of the receptor changes? variable or constant?

follicle

In the spleen, marginal zone surrounds the

10%

what percent of B cells make it to the periphery?

true

(true/false) peripheral tolerance contains both processes of positive and negative selection

negative selection

in peripheral tolerance, binding equals death, 55-75% B cells are removed; what type of selection is this?

BAFF

pro-survival signal for B cells produced by dendritic cells that live in the follicle

positive

in peripheral tolerance of B cells, Low binding to ligands = survival; what type of selection is this?

false (some binding is good)

(true/false) BCRs that bind to self antigen at all in peripheral tolerance are always eliminated, either through apoptosis or anergy

B-2

these types of cells are mature follicular B cells; migrate from lymphoid tissue to tissue to blood and back again; 1-3% of B cells make it to this stage

DAG

if T1 cells bind to self-antigen in peripheral tolerance in B cells, then Ca is produced but not this compound, which leads to death

diacylglycerol

DAG = ?

Ca and DAG

if T2 binds to self antigen (low affinity), which two compounds form, leading to survival of the B cell

Follicular, B-1, marginal zone

three types of naive B cells

B-1, marginal zone

which two types of B cells don’t need T cells to activate?

B-1

which type of B cell primarily produces IgM, produces natural antibodies, and close by areas where antigen might be present, like lung and gut?

marginal zone

which type of B cell is specialized to respond to blood borne antigens entering the immune system though the spleen?

Frank MacFarlane Burnet

who came up with the Clonal selection hypothesis (1957)?

incorrect (deleted all the time)

According to Burnet’s hypothesis, B cells with receptors for self antigen are deleted during embryonic development. this is _______ (correct/incorrect) because

incorrect (somatic hypermutation)

According to Burnet’s hypothesis, on stimulation, each cell will proliferate to generate a clone of cells bearing the same BCR as original; this is _____ (correct/incorrect) because

memory

these types of B cells remember the antigen for later

plasma

these types of cells which come from B cells release their antibodies to circulate in blood

follicular dendritic cells

these cells secrete BAFF survival signal

resident and circulatory

there are two types of B cells; one kind stays in the follicle, the other kind moves throughout bloodstream and lymph

cognate

A BCR’s corresponding antigen is known as its ______ antigen

BCR binds with antigen, phagocytosis of antigen, antigen presentation in MHC II, T cell involvement, clonal expansion, somatic hypermutation, affinity maturation, isotype switching

name the eight steps of B cell activation

antigen, BAFF

follicular dendritic cells present/give which two things to B cells?

antigen + MHC II

TCRs bind to what two things on a B cell during the T cell involvement step of B cell activation?

CD40:CD40L

what on the B cell binds to what on the T cell in the immunological synapse?

CD4

this on helper T cells binds to MHC II but not the antigen

cytokines

binding at the immunological synapse and CD4 leads to the release of these, which are relevant to B cell activation

rippling of membrane

Binding of BCR induces membrane changes causing the cell to increase in size for a few minutes to efficiently scan for antigens nearby; this is known as

T independent responses

TI-1 antigen and TI-2 antigen in B cells are examples of what, which are generated upon exposure to multivalent/polymerized antigen?

TI-1

this kind of T independent response is known as an “extra activation signal"; Antigen binds to B cells through PRRs and BCR

TI-2

this kind of T independent response is known as an “Extensive activation signal”; Cross linking large numbers of BCRs and sometimes complement receptor of B cell binding to complement

clonal expansion

which step of B cell activation?

• Massive proliferation of the stimulated B cell

• An army of B cells are made

• Occurs in the dark zone of germinal center

dark zone of germinal center

where does B cell clonal expansion occur?

Activation induced Cytidine Deaminase

AID in B cell activation stands for

somatic hypermutation

which step of B cell activation?

• During the clonal expansion, an enzyme called AID (Activation induced Cytidine Deaminase) gets activated in all the cells and causes point mutations in variable region

• Slightly different BCR per B cell

• “Quasi clonal”

AID

which enzyme is responsible for somatic hypermutations?

affinity maturation

which step of B cell activation?

• Clones of B cells enter the circulation and lymph tissue (migrate to light zone)

• Increased B cell survival of BCR that binds to antigen best + replication and transition to plasma cell

apoptosis

weak/no BCR binding after somatic hypermutation leads to

isotype switching

what step of B cell activation?

• In plasma cells, the Constant /Fc portion of the heavy chain of the antibody changes to accommodate antibody function

• Constant region of Ig molecule changes in order to be secreted

plasma cells

Immunoglobulin producing machines; Transcription factors in a regulatory network dictate the fate of antigen activated B cells

BCR

a membrane bound antibody with associated 2 alpha and beta molecules; Help transmit an intracellular signal from outside of the cell after antigen binds to antibody

C domain, V domain, hinge region

3 parts of an antibody

hinge region

part of an antigen that allows antigen binding arms of antibodies to flex inward and outward

proline residues

what component of the hinge region makes it flexible?