Chapter 10 Bursa/Bone Marrow- Derived Cells (B-cells) Flashcards
Where do B cells mature in birds?
Bursa Fabricus (BF)
In mammals early events of B cell development begin where?
Bone Marrow or Peyers Patches
When immature leaves the Bone marrow or Peyers Patches where do they go?
Immature B cells leave these organs and complete their maturation in the spleen before recirculating to seed all the peripheral lymphoid organs.
Does B cell Lymphopoiesis occur throughout life?
Yes, though it gradually decreases in numbers with age.
B-cells constitute how much or recirculating pool of lymphocytes?
10-25%
Are B cells short lived or long lived?
short lived
Are memory B cells short lived or Long lived?
Long lived
What does the BCR complex consist of?
IgM and IgD and two invaient proteins that are disulfide linked to eachother (Ig alpha(CD79) and IgBeta(CD79b))
All BCRS recognize only a single antigen, which is known as?
Clonotypic
Since BCRs have a short cytoplasmic tail who transduces the signals to the B cell nucleus?
CD79 molecules
which are also required for the surface expression of IgM and IgD
The gene family on chromosome 14 codes for what? and consist of what?
Ig heavy chain
consist of 200Vh 30Dh 6Jh and 9Ch
Gene family on chromosome 2 codes for and consist of?
K chain
consist of 100 Vk 5Jk 1Ck
Gene family on chromosome 22 codes for and consist of?
lamda chain
consist of 100V 6J 4C
If the first rearrangement of the chain is nonproductive what happens?
Then it proceeds to the second allelic chromosome
In recombination of the IgH chain if both alleles undergo no-productive recombination what happens?
the developing B Cell cannot produce antibodies and undergoes apoptosis.
The production of mature RNA requires what?
Both recombination of DNA segments and splicing of primary RNA transcript.
Translation of the u Heavy chain mRNA leads to the production of what?
u protein
The production of a u protein triggers what?
IgL chain gene rearrangement
IgL chain rearrangement begins with what?
the k light chain, if the rearrangement is successful and functional k light chains are synthesized, irreversible inhibition of lambda gene segments occur.
If non functional rearrangement occurs with K and lambda chain what happens?
the B cell undergoes apoptosis.
What mechanisms account for B cell diversity?
Somatic recombination of multiple germline gene segments
Junctional diversity, Base deletion and N-nucleotide additions
Who expresses TdT?
the pro-B cell only during the stage of IgH gene rearrangement
what chain shows N-region diversity?
IgH chain
What do Bone marrow stromal cells make?
IL-7
Why is IL-7 so important?
it is important for T and B cell maturation.
What does the Progenitor B cell express?
IgAlpha (CD79a) and IgBeta(CD79b)
what does the Precursor B cell continue to express and what activity does it terminate?
continued expression of RAG-1 and RAG-2 and termination of TdT activity.
In the synthesis of the IgM heavy chain the heavy chain pairs with what?
pairs with the surrogate light chain
Where is heavy chain and surrogate line chain pairs expressed at?
on the Pre-B cell surface in association with the IgAlpha and IgBeta molecules to make the BCR
Signals generated through the Pre- B cell receptor are essential for?
Continued development of pre-B cell
Pre B cell receptor signaling results in what events?
- ) survival and proliferation of pre-B cell
- ) inhibition of Vh to DhJh rearrangement of the other heavy chain allele ( allelic exclusion)
- ) termination of surrogate light chain transcription
- ) initiation of light chain (K or lambda) gene rearrangement
When is the cell called an immature B cell?
After rearrangement of the light chain genes, IgM containing both heavy and light chains is expressed on the cell membrane. The cell sheds its pre- B cell receptors and is now called an immature B cell.
What happens in the selection of the B cell repertoire?
if an immature B cell that expresses high-affinity BCR for self antigen binds the antigen in the bone marrow:
- ) it dies by apoptosis (clonal deletion)
- ) it becomes anergic ( long lasting inactivation)
- ) may undergo receptor editing.
What is receptor editing?
Its B cells second chance to rearrange the light chain.
this process attempts to rescue a self reactive B cell from undergoing apoptosis.
The B cell reactivates RAG1 and RAG2 genes and begins further rearrangement of the light chain.
Do TCRs undergo receptor editing?
No they do not
Where do immature B cells go to after leaving the Bone marrow
They migrate to the spleen
Can the TCR bind a soluble antigen?
Can the BCR bind a soluble antigen?
TCR cannot it must be displayed on MHC
BCR can
what are the B cell coreceptor additional signal transduction molecules associated with BCR?
CD21 CD19 CD81
what are the co-stimulatory molecules that interact with CD28 and CD152?
B7 (CD 80 and CD86)
The B cell coreceptor complex is made up of what three cell surface molecules?
CR2 (CD21), CD 19, CD81
what is CR2?
a complement receptor that binds complement component, C3d
Where does Helper T cell- B cell interactions occur at?
the junction of the cortex and paracortex
Activated B cells migrate back into where?
primary follicles
What are the net results of Response of B cells to T- dependent (protein) antigens?
The net results are induction of B cell clonal expansion, isotype switching, affinity maturation, and differentiation into plasma cells or memory B cells
What is CD40?
a costimulatory receptor for B cells which Binds to CD40L on Th cell
What does CD40 promote?
it promotes the expression of co-stimulatory molecules, growth and differentiation of B cells and together with cytokines, isotype switching, affinity maturation, and development of memory cells.
What does IL-2 do?
Clonal expansion
IL-4 and Il-5 also contribute to B cell proliferation
What is isotype (Class) switching?
A change in antibody class that occurs during the course of an immune response to a protein antigen as a result of heavy chain gene switching.
How can you remember the immunoglobulin isotypes that can be switched?
GAMED!
IgG IgA IgM IgE IgD
What determines the effector function of an immunoglobulin molecule?
it is determined by the isotype of its heavy chain C region.
What is Affinity maturation?
the process that results in an increase in the affinity of specific antibody for its antigen and is the result of somatic mutations of the previously rearranged Ig V(D)J genes, followed by selective survival of the B cells producing the antibodies with the highest affinity.
Affinity maturation occurs only in ______ _____ responses to protein antigens, since CD40-CD40L and T helper cell derived cytokines regulate somatic mutations.
Humoral immune responses
Who does the selection of high-affinity B cells?
Follicular dendritic cells.. (FDCs)
Do FDCs present antigens to helper T cells?
they are found in lymphoid follicles of the lymph nodes, spleen and MALT. FDCs are non phagocytic cells and do not present antigens to helper T cells.
What is the net result of the selection of high affinity B cells?
The net result of this selection process is a population of B cells that become memory B cells with high affinity BCRs or B cells that become plasma cells that produce antibodies with significantly higher affinities for antigen than the antibodies produced by the same clones of B cells earlier in the immune response.
How long do Plasma Cells live?
Short lived 3-6 days
Some plasma cells migrate places where do they migrate?
some may migrate from the peripheral lymphoid organs to the bone marrow, where they continue to produce low levels of antibodies for many years.
Where a plasma cells found at in peripheral lymphoid organs?
- Red pulp areas of the spleen
- Medulla of the lymph nodes
- MALT (lamina propria of intestinal and respiratory tracts
- Bone marrow sinusoids
What do the heavy chains of Igs produced by plasma cells lack?
the transmembrane hydrophobic amino acids
All anitbodies secreted by a single plasma cell have the same ____ and _____
specificity and isotype
What is a multiple myeloma?
a tumor of plasma cells
where do Myelomas come from?
arising as a result of a random mutation in a single B cell.
How do you test for light chains?
precipitate then redissolve
Are memory Cells long lived cells?
they are functionally inactive long lived cells ( months to years)
Whose antigenic does for stimulation is lower Memory cells or Naïve B cells?
Lower does to stimulate memory Cells
T-independent antigens are able to provoke Ig production in the absence of??
Helper T cells
Responses to most T-independent antigens consist mainly of ______ antibodies
IgM antibodies of low affinity and do not show significant heavy chain class switching, affinity maturation or memory
What are Lymphocyte mitogens?
Agents capable of inducing cell division in a high percentage of T and B cells.
examples of B cell mitogens?
LPS, Protein A
Examples of T cell mitogens?
Phytohemagglutinin, Concanacalin A
Example of T and B cell mitogens?
Pokeweed
What are B cells secreted products?
Soluble immunoglobulins
What are T cells secreted products?
Cytokines
What are important surface antigens for B cells?
Immunoglobulins
What are important surface antigens for T cells?
CD2, CD3, CD4, or CD8
