B lymphocytes Flashcards
B lymphocytes are the precursors of what important cells that produce antibodies?
Plasma cells
All antigen-unstimulated B lymphocytes have what two immunoglobins in their plasmalemma?
IgM and IgD
Can B lymphocytes bind anitgens without MHC proteins?
Yes
Each B lymphocyte is specific for how many antigens?
one
True or false: B cell are genetically engineered and produced only when exposed to antigens
False-B cell clones reactive to >109 antigens exist in the body at all times, without the need for exposure to these antigens.
How long does the primary response take?
7-10 days
Which antibody type is produced in the greatest amount in the primary response?
IgM
How long does a secondary immune response take place?
2-3 days
Which antibody is produced in the greatest amount in the secondary immune response?
IgG
Is the overall antibody count higher or lower in secondary immune responses?
Higher
What happens to the affinity of antibodies the longer an infectious process occurs?
Gets more specific, and binds better
What is the cell that is the precursor to all blood cells?
Stem cells
DO stem cells conduct immunoglobin production?
No
What are the 5 stages of B cell maturation?
- Stem cell
- Pre-B cell
- Immature B cell
- Mature B cell
- Activated B cell
Are pre-B cells responsive to antigen?
No
Pre-B cells do not have mature immunogoblin yet, but what do they have?
cytoplasmic mu-heavy chains, which will eventually become membrane-bound IgM
In what stage do antigens become expressed on the surface of B cells?
Immature B cell stage
What antigen(s) is/are present in the immature B cell stage?
IgM
What happens to immature b cells if they encounter an antigen? Why do they do this?
Death, to prevent reaction to self proteins
At which stage in B cell development are the cells outside the bone marrow?
Mature B cell stage
Mature B cells express two antibodies on their membrane. Which class of immunoglobins are they from?
IgM and IgD
Are the IgM and IgD antigens on mature B cells specific for the same or different antigens?
The same–bad if not
What happens when B cells encounter an antigen that is specific for its receptor?
Activation/Mitosis
True or false: a high level of antigens are produced, but are of low specificity when B cells are initially activated
False–both low amounts, and low specificity
During which stage of B cell development can heavy chain isotype switching occur?
At the activated B cell stage
True or false: switching of light chains never occurs in the activated B cell stage
True
What are the two major cell types that B cells can differentiate into?
Plasma cells or memory cells
Where are memory B cells found?
Recirculate through secondary lymphoid tissue throughout their life
What specific antibodies do plasma cells secrete?
one of the heavy chain isotypes (IgG, IgM, IgA or IgE).
Where are plasma cells found?
in lymphoid organs and bone marrow and not generally in the peripheral blood.
What are the histological features of plasma cells?
Elongated cell, eccentric nucleus, abundant cytoplasm, and perinuclear halo.
How many antibodies can be secreted per second by plasma cells?
3000-4000
What percent of protein synthesis of plasma cells are devoted to antibody generation
Up to 40%
How do B and T cells react together?
B cells present antigen bits to T cells via CD4+/class II MHC
Do B and T cells that cooperate together respond to the same antigen?
Usually different
What is the time frame for antigen presentation from B cells?
1-6 hours
Can nonprotein antigens be complexed to MHC proteins for T cell activation?
Nope
True or false: The epitope that the B cell binds is usually different from what is presented to T-helper cells.
True
What happens when B and T lymphocytes interact?
B and T cells express costimulatory proteins on their cell surface that must interact in order to get T lymphocyte activation and the consequent B lymphocyte activation leading to antibody production.
What are the proteins that B cells produce that aid interact with T cells? What is the protein that T cells express for this?
B7 and CD40 which interact with the T cell protein CD28 and CD40L respectively
When B7:CD28 and CD40L:CD40 interactions occur along with the binding of class II MHC-bound peptide through the T cell antigen receptor, what happens?
T cells are activated and release cytokines that, along with CD40L:CD40 interactions, activate B cells to differentiate into antibody-producing plasma cells.
How do B cells compareto macrophages in terms of their ability to process antigens?
Less efficient due to less lysosomes, but they are more specific
What do B cells require to respond to antigens?
Th lymphocytes
What are the “thymus dependent” antigens?
Ones that respond to proteins, and require the use of T helper cells
What are thymus independent antigens?
B cells responses to non-protein antigens, and thus cannot utilize helper T cells
What are the two types of TI antigens?
TI 1
TI 2
What are TI-1 antigens?
Antigens that bind to non-immunoglobin receptors on B cells, and promote polyclonal expansion
What are TI-2 antigens?
Antigens that bind through B cell surface immunoglobin, and activate antigen specific B cells
What does not occur with TI antigens that does occur with TD antigens?
- memory cell generation
- isotype switching
- affinity maturation occurs.
LPS is an example of what type of TI antigen? What does this complex associate with?
TI-1
associates with B cell surface CD14 and Toll-like receptor-4
Antigens that crosslink B cell surface immunoglobulin signal B cell activation through what proteins?
Igα and Igβ
What is the function of Igα and Igβ in B cells?
Functions the same as CD3 proteins in T cells
How many of each chain type comprise each antibody isotope?
two heavy chains (of one of the five isotypes) and either two kappa or two lambda light chains.
True or false: the kappa light chain, lambda light chain, and heavy chain are each encoded by different chromosomes
True
What are the V regions of immunoglobin genes? Where are they found?
V= Variable regions at the 5’ end of each string. Signal genes here encode a protein sequence used to guide a protein to the ER.
What are 3’ to the V regions, and within the heavy chain and kappa kight chain loci?
J (“joining”) regions
What is located between the V and J regions of the genome?
Heavy chain D regions
Where are the C (constant) regions of immunoglobin found?
at the 3’ end of each heavy and light chain string of gene segments
The variable region of the immunoglobulin heavy chain forms what part of the antibody?
antigen binding site
The variable region of the heavy chain gene is generated by which segments?
generated by assembling V, D, and J segments of DNA.
The variable region of the light chain genes are generated by assembling what segments of DNA?
V and J (no D like heavy has)
What are the four main mechanisms that account for the diversity seen in the immunoglobin repertoire?
- Combinatinoal diversity
- Junctional diversity
- Heavy and light chain combining
- Somatic point mutations
What is combinational diversity?
Different copies of gene segments exist that can be rearranged in many ways.
What is junctional diversity?
Nucleotide addition and removal occurs at the joints between gene segments that are recombined.
What is the normal configuration of the imunoglobin genes that are found in every nucleated cell throughout the body, except in B cells?
Germline DNA
What is recombinase, and what is its function in B cell development?
It causes the looping out of DNA sections followed by excision of the intervening sequences, and ligation of the DNA.
What is the gene that encodes recombinase? Mutations in this gene leads to what?
RAG1 and RAG2
SCID results if there are mutations
What ensures that the progeny of a B cell will not mutate and express a different Ig gene?
Genes are irreversibly lost in development
Which rearranges first: the heavy or the light chain locus?
Heavy chain
What is the first step in rearranging the heavy chain locus?
Randomly chosen D and J segments are brought together, with intervening sequences deleted
What happens in heavy gene rearrangement, after D and J segments are brought together?
V region gene segment is randomly sleected, and placed 5’ to the DJ segment. Intervening segment is deleted
What is the function of the enzyme terminal deoxynucleotidyl transferase (TdT)? Where does it act?
Randomly adds nucleotides in the joint region between gene segments in the VDJ region
What separates the VDJ segment from the first C region gene (C-mew)?
An intron region
Translation of the mRNA gives rise to cytoplasmic -heavy chain protein occurs in what stage of B cell maturation?
Pre-B cell stage
If the rearrangement of the 1st heavy chain gene is nonproductive, what happens?
The other allele is used
If both rearrangements of heavy chain are nonproductive what happens?
Apoptosis
What is the first step in light chain gene rearrangement?
A V region gene segment is randomly selected and placed next to a J region gene segment to form a VJ segment, with intervening sequences being subsequently deleted.
What happens in light chain gene rearragement after a VJ segment is created?
Splicing out introns
What separates the VJ segment of the light chain, from the C region?
An intron
An excess of kappa light chains might suggest that the patient has what?
a B cell tumor that is producing a large amount of monoclonal antibody utilizing a kappa light chain or some other type of nonmalignant lymphoproliferative disorder.
What is allelic exclusion?
if the 1st rearrangement is productive then genes on other chromosome won’t be rearranged
Why is there no “choosing” of constant regions in light chain gene recombination, like there is in heavy?
Kappa and lambda light chain gene segments are located on different chromosomes
Heavy chain located on same, so can splice out which ones not needed
What are the antibodies that are expressed on resting B cells?
IgM and IgD
The primary RNA transcript for the IgM and IgD antibodies present on the surface of B cells has which regions? How does this contribute to the anitbody expression o the cell?
VDJ regions coupled to both C(mew) and C(delta) region
Thus splicing can splice out one of the C regions but retain the VDJ segment
How do antibodies that are expressed on the cell surface of B cells become secreted?
the transmembrane and cytosolic sequences are spliced out of the primary RNA transcript
What is the first step the B cell takes in switching antibody isotypes?
Stimulation by antigens
How can gene splicing lead to isotype switching in B cells?
A long primary RNA transcript containing VDJ regions connected to many or all CH genes is produced, followed by alternative RNA splicing.
How can gene deletion lead to isotype switching in B cells?
deletion of intervening CH region genes to align VDJ regions with a particular CH gene occurs
What are switch regions in the DNA segment?
Regions that allow DNA recombination to occur between heavy chain constant region gene segments
What determines which antibody a B cell will switch to?
The array of T cell cytokines to which the B cell is exposed
IL-4 cytokines induce B cells to switch to what antibody? IL-5?
IL-4 = IgE
IL-5 = IgA
Antibodies in a secondary immune response have a (higher or lower) average affinity than those in a primary immune response.
Higher
What alters the affinity of antibodies in a secondary immune response?
small somatic mutations in the V region genes to alter the strength of binding of an antibody
Are C regions changed when antibodies increase in affinity?
No
Why is secondary immune response much more sensitive to stimulation?
memory B cells express a higher affinity antigen receptor
How are B cells that express higher affinity anitbodies selected for?
their increased ability to bind antigen increases their chance of stimulation by follicular helper T cells (TFH), leading them to out compete other B cell types
If a B cell receives interferon gamma, which antibodies will it produce?
IgG1 and IgG3
If a B cell receives IL-4, what antibodies will it produce?
IgE IgG4
