MIMG C185A Exam | Questions and
Complete Answers | 100% Pass
What role does B cells play in? - Correct Answer - Innate and adaptive immunity
What are the 3 known subsets of B cells and what immunity do they play in? - Correct
Answer - B1: Innate immunity
- B2 (conventional): Adaptive Immunity
- Marginal Zone B cells: Innate and Adaptive immunity
What subsets is B-1 B cells divided into and what do they both contain? - Correct
Answer - B-1a expressing protein CD5
- B-1b that do not express CD5
- Both are high in IgM
- Important to know B-1 B cells sometimes express CD5 (marker for T cells)
Describe B-1 B cells and their location? - Correct Answer - Long-lived and self-renewing
- Develops early in ontogeny from fetal omentum and liver
- After birth, stems cell for B-1 are NOT present in bone marrow
- In adults, they are found predominately in peritoneal and pleural cavities
- Rare in spleen and absent from lymph node and peripheral blood
Describe the variability of the B-1 B cells and what they produce - Correct Answer -
Limited V region repertoire
- Lots of self-reactivity
- Recognition of bacterial antigens (phosphorylcholine)
- Broad specificity and low affinity
- Produce specifities encoded in germline with no N region insertion and little somatic
mutation
- Produce large amounts of antibody (>50% of all antibodies in serume)
- Responsible for majority of non-immune serum IgM and constribute to resting IgA
- If you immunize your reaction, there will be IgM present that is non-immune cause of
B-1 B cells
What type of responses does B-1 B cells have and do they require T cell help? - Correct
Answer - Does not require T cell help
- TI-2: make antibody response to polysaccharide Ags found on bacteria
- Plays role in innate response to infection (Abs mostly germline encoded)
- Rapid response: Makes Abs within 48 hours of antigen exposure (due to bacterial
antigen)
- Without T cell help, do not isotype switch (although some IgA) and no memory
What is the origin of B-1 B cells and what role does it play in autoimmune disease? -
Correct Answer - Hypothesized to be primitive B cells
- In mice, at birth predominately B-1 but later B-2 dominates
,- Abundant in autoimmune disease (specficity is often self-reactive)
- B-1 cells origin for human chronic lymphocytic leukemia, typically express CD5
B-2 B cells arise from where and how do they generate and play a role in the immune
response? - Correct Answer - Principle B cells in secondary lymphoid organs (spleen,
lymph nodes)
- Arise from fetal liver and bone marrow in adult
- Stem cells continually generate
- Principal B cells in adaptive immune response
Explain the variability of B-2 cells and if they need T cell help or not? - Correct Answer -
Have extensive variable region repertoire generated somatically
- Requires T cell help, therefore have isotype swtich and memory
- Recirculates through B cell rich lymphoide follicles
- TD antigen responses in germinal center
Where are Marginal zone (MZ) B cells found and what role do they play? - Correct
Answer - Originate in bone marrow from same precursors as B-2 B cells
- Found in marginal zone of the spleen
- Participate both in TI and TD antibody responses
- Contribute to natural IgM present
- Memory B cells also found in marginal zone
- Contain somatic mutations (like B-2)
- Response to blood-borne antigens
- Produce antibody response to polysaccharide Ags of blood-borne bacteria
What two types of B cells are developed in the bone marrow and what are found in the
Marginal Zone of the spleen and of the Follicular? - Correct Answer - Two types of B
cells develop in the bone marrow: B-2 and MZ-B
- Marginal Zone: B cells found here in spleen --> B1 and MZ B cells participate in TI
response making natural IgM present (innate). MZ B cells participate in TD responses
(adapative) too
- Follicular: Majority of B cells that recirculate through B cell rich lymphoid follicles and
participate in TD Ag Response
What happens in B cell development in the bone marrow? - Correct Answer - In fetus,
before there is a BM, hematopoiesis takes place in the liver
- Fetal live shuts off, stem cells migrate to bone marrow and Ig gene rearrangement
occurs for B cell differentiation
- At bone marrow, stem cells persist around periphery of hollow bone space
- Stem cells divide and migrate toward large vein in center of the bone (require bone
marrow matrix to divide)
- Spongy matrix of reticular cells, macrophages, and other supporting cells produce
growth/ differentiation factors to guide development
Antigen- Independent - Correct Answer
,What signal allows Pro-B cells to differentiate into immature B cells? - Correct Answer -
Adhesion molecules VLA-4 on Pro-B cells interacts with VCAM-1 receptor on bone
marrow stromal cells, signaling for development
- c-Kit on Pro-B cells interact with stem-cell factor (SCF) on bone marrow stromal cell
activating c-Kit, causing Pro-B to divide into Pre-B cell
- Pre-B cells express IL-7 receptor and IL-7 produced by stromal cells drive maturation.
Immature B cells then express IgM on their surface
What are the two phases of B cell maturation? - Correct Answer - Antigen Independent
- Antigen Dependent
What happens in the Antigen Independent stage? - Correct Answer - B220 marker on
all B cell until they become plasma cells
- Pro-B cell: Joining of DH and JH (requires RAG-1/RAG-2 enzymes) and terminal
transfer (TdT) for added nucleotide diversity. Also Germline kappa/lambda join, but no
function V region so no function heavy chain
- Pre-B cell: Rearranged VH-DH-JH with surrogate L chain (Still need RAG and TdT). L
chain needed to get expression of pre-B cell receptor on surface
- Immature B cell: Heavy chain + kappa/lambda (V-J) chain --> Requires RAG only not
TdT (not present when L chain is rearranging). Immature expresses IgM
- Mature B cell: Express IgM and IgD simultaneously and leave bone marrow into
periphery (spleen and lymph nodes as well)
- Activated B cell also have B220
- All in Bone cell development
What happens during the Antigen Dependent stage? - Correct Answer - Mature B cells
leave out into periphery to be activated
- Develops with T cell help into Plasma cell (isotype switch / memory formation)
- Requires Antigen
- In periphery, somatic hypermutation takes place in periphery and germinal centers,
doesn't take place in initial development
- Plasma cells don't isotype switch and don't change binding specificity (lacks B220 and
membrane Ig, so cannot receive any further signals since it doesn't need to)
What happens during knock-out RAG1 / RAG2? - Correct Answer - BCR and TCR
remain unrearranged
- B and T cell development arrested
How does B cell receptor get activated from the use of its surface receptor? - Correct
Answer - Surface Ig is the receptor for the B cell
- Ig-alpha and Ig-beta assocaite with membrane bound heavy chain
- Ig-a and Ig-B have immunoreceptor tyrosine-based activation motifs (ITAM)
- Activation of BCR leads to phosphorylation of ITAMs by Src family kinases and
recruitment and activation of Syk kinase, having signal transduction
, What happens when you knock out Ig-a and Ig-B? - Correct Answer - Cells lacking Ig-a
or Ig-b do not have surface Ig and arrest in B cell development
- No affect on T cell development
- B and T cells have CD43+, but immature B cells lose CD43
What is the composition of the surrogate L chain as it associates with the BCR? -
Correct Answer - L chains comprised of Vpre-B (variable region) and a constant region
- L chain for lambda and another L chain for kappa
- Associates with mieu heavy chain
What happens when surrogate L chain expression is blocked? - Correct Answer -
Blocks B cell differentiation at the Pre-B stage because it cannot express Ig on surface
How does the surrogate L chain interact with the B cell to differentiate into an immature
B cell? - Correct Answer - ITAMs associated with heavy chain gets to surface because
of surrogate L chain
- Crosslinking of stromal cell ligand gives signal for allelic exclusion and allow VH-DH-
JH to form
- Induces VL-JL light chain rearrangement
- Now have immature B cell and crosslinking by antigen causes Activation or
Death/Receptor editing
What is the ligand for Pre-BCR expressed by stromal cells and what is it used for? What
Ig is requried? - Correct Answer - ligand for pre-BCR is galectin-1 expressed by stromal
cells
- BCR signaling important for establishing allelic exclusion and initiating L chain
rearrangement
- Both require expression of membrane form IgM
Expression of functional heavy chain on the membrane inhibits what and initiates what?
- Correct Answer - Inhibits heavy chain rearrangement
- Transgenic mice with human IgM versus WT mice: showed that human heavy chain
IgM stops expression of mice IgM, making only human IgM
- Initiates L chain rearrangement despite no heavy chain rearrangement
- Need functional heavy chain expressed on surface of B cell for L chain rearrangement
(membrane IgM)
What does Allelic exclusion do and how does it occur? - Correct Answer - Allelic
exclusion guarantees that a B cell makes only one functional, non-self reactivity
antibody
- Synthesis of functional H chain turns off H chain rearrangement and turns on L chain
rearrangement
- Synthesis of functional L chain turns off gene rearrangement
- In mice: kappa light chains rearrange first, if both alleles are non-functional,
rearrangement of lambda light chain takes place, if both fail, then die
Complete Answers | 100% Pass
What role does B cells play in? - Correct Answer - Innate and adaptive immunity
What are the 3 known subsets of B cells and what immunity do they play in? - Correct
Answer - B1: Innate immunity
- B2 (conventional): Adaptive Immunity
- Marginal Zone B cells: Innate and Adaptive immunity
What subsets is B-1 B cells divided into and what do they both contain? - Correct
Answer - B-1a expressing protein CD5
- B-1b that do not express CD5
- Both are high in IgM
- Important to know B-1 B cells sometimes express CD5 (marker for T cells)
Describe B-1 B cells and their location? - Correct Answer - Long-lived and self-renewing
- Develops early in ontogeny from fetal omentum and liver
- After birth, stems cell for B-1 are NOT present in bone marrow
- In adults, they are found predominately in peritoneal and pleural cavities
- Rare in spleen and absent from lymph node and peripheral blood
Describe the variability of the B-1 B cells and what they produce - Correct Answer -
Limited V region repertoire
- Lots of self-reactivity
- Recognition of bacterial antigens (phosphorylcholine)
- Broad specificity and low affinity
- Produce specifities encoded in germline with no N region insertion and little somatic
mutation
- Produce large amounts of antibody (>50% of all antibodies in serume)
- Responsible for majority of non-immune serum IgM and constribute to resting IgA
- If you immunize your reaction, there will be IgM present that is non-immune cause of
B-1 B cells
What type of responses does B-1 B cells have and do they require T cell help? - Correct
Answer - Does not require T cell help
- TI-2: make antibody response to polysaccharide Ags found on bacteria
- Plays role in innate response to infection (Abs mostly germline encoded)
- Rapid response: Makes Abs within 48 hours of antigen exposure (due to bacterial
antigen)
- Without T cell help, do not isotype switch (although some IgA) and no memory
What is the origin of B-1 B cells and what role does it play in autoimmune disease? -
Correct Answer - Hypothesized to be primitive B cells
- In mice, at birth predominately B-1 but later B-2 dominates
,- Abundant in autoimmune disease (specficity is often self-reactive)
- B-1 cells origin for human chronic lymphocytic leukemia, typically express CD5
B-2 B cells arise from where and how do they generate and play a role in the immune
response? - Correct Answer - Principle B cells in secondary lymphoid organs (spleen,
lymph nodes)
- Arise from fetal liver and bone marrow in adult
- Stem cells continually generate
- Principal B cells in adaptive immune response
Explain the variability of B-2 cells and if they need T cell help or not? - Correct Answer -
Have extensive variable region repertoire generated somatically
- Requires T cell help, therefore have isotype swtich and memory
- Recirculates through B cell rich lymphoide follicles
- TD antigen responses in germinal center
Where are Marginal zone (MZ) B cells found and what role do they play? - Correct
Answer - Originate in bone marrow from same precursors as B-2 B cells
- Found in marginal zone of the spleen
- Participate both in TI and TD antibody responses
- Contribute to natural IgM present
- Memory B cells also found in marginal zone
- Contain somatic mutations (like B-2)
- Response to blood-borne antigens
- Produce antibody response to polysaccharide Ags of blood-borne bacteria
What two types of B cells are developed in the bone marrow and what are found in the
Marginal Zone of the spleen and of the Follicular? - Correct Answer - Two types of B
cells develop in the bone marrow: B-2 and MZ-B
- Marginal Zone: B cells found here in spleen --> B1 and MZ B cells participate in TI
response making natural IgM present (innate). MZ B cells participate in TD responses
(adapative) too
- Follicular: Majority of B cells that recirculate through B cell rich lymphoid follicles and
participate in TD Ag Response
What happens in B cell development in the bone marrow? - Correct Answer - In fetus,
before there is a BM, hematopoiesis takes place in the liver
- Fetal live shuts off, stem cells migrate to bone marrow and Ig gene rearrangement
occurs for B cell differentiation
- At bone marrow, stem cells persist around periphery of hollow bone space
- Stem cells divide and migrate toward large vein in center of the bone (require bone
marrow matrix to divide)
- Spongy matrix of reticular cells, macrophages, and other supporting cells produce
growth/ differentiation factors to guide development
Antigen- Independent - Correct Answer
,What signal allows Pro-B cells to differentiate into immature B cells? - Correct Answer -
Adhesion molecules VLA-4 on Pro-B cells interacts with VCAM-1 receptor on bone
marrow stromal cells, signaling for development
- c-Kit on Pro-B cells interact with stem-cell factor (SCF) on bone marrow stromal cell
activating c-Kit, causing Pro-B to divide into Pre-B cell
- Pre-B cells express IL-7 receptor and IL-7 produced by stromal cells drive maturation.
Immature B cells then express IgM on their surface
What are the two phases of B cell maturation? - Correct Answer - Antigen Independent
- Antigen Dependent
What happens in the Antigen Independent stage? - Correct Answer - B220 marker on
all B cell until they become plasma cells
- Pro-B cell: Joining of DH and JH (requires RAG-1/RAG-2 enzymes) and terminal
transfer (TdT) for added nucleotide diversity. Also Germline kappa/lambda join, but no
function V region so no function heavy chain
- Pre-B cell: Rearranged VH-DH-JH with surrogate L chain (Still need RAG and TdT). L
chain needed to get expression of pre-B cell receptor on surface
- Immature B cell: Heavy chain + kappa/lambda (V-J) chain --> Requires RAG only not
TdT (not present when L chain is rearranging). Immature expresses IgM
- Mature B cell: Express IgM and IgD simultaneously and leave bone marrow into
periphery (spleen and lymph nodes as well)
- Activated B cell also have B220
- All in Bone cell development
What happens during the Antigen Dependent stage? - Correct Answer - Mature B cells
leave out into periphery to be activated
- Develops with T cell help into Plasma cell (isotype switch / memory formation)
- Requires Antigen
- In periphery, somatic hypermutation takes place in periphery and germinal centers,
doesn't take place in initial development
- Plasma cells don't isotype switch and don't change binding specificity (lacks B220 and
membrane Ig, so cannot receive any further signals since it doesn't need to)
What happens during knock-out RAG1 / RAG2? - Correct Answer - BCR and TCR
remain unrearranged
- B and T cell development arrested
How does B cell receptor get activated from the use of its surface receptor? - Correct
Answer - Surface Ig is the receptor for the B cell
- Ig-alpha and Ig-beta assocaite with membrane bound heavy chain
- Ig-a and Ig-B have immunoreceptor tyrosine-based activation motifs (ITAM)
- Activation of BCR leads to phosphorylation of ITAMs by Src family kinases and
recruitment and activation of Syk kinase, having signal transduction
, What happens when you knock out Ig-a and Ig-B? - Correct Answer - Cells lacking Ig-a
or Ig-b do not have surface Ig and arrest in B cell development
- No affect on T cell development
- B and T cells have CD43+, but immature B cells lose CD43
What is the composition of the surrogate L chain as it associates with the BCR? -
Correct Answer - L chains comprised of Vpre-B (variable region) and a constant region
- L chain for lambda and another L chain for kappa
- Associates with mieu heavy chain
What happens when surrogate L chain expression is blocked? - Correct Answer -
Blocks B cell differentiation at the Pre-B stage because it cannot express Ig on surface
How does the surrogate L chain interact with the B cell to differentiate into an immature
B cell? - Correct Answer - ITAMs associated with heavy chain gets to surface because
of surrogate L chain
- Crosslinking of stromal cell ligand gives signal for allelic exclusion and allow VH-DH-
JH to form
- Induces VL-JL light chain rearrangement
- Now have immature B cell and crosslinking by antigen causes Activation or
Death/Receptor editing
What is the ligand for Pre-BCR expressed by stromal cells and what is it used for? What
Ig is requried? - Correct Answer - ligand for pre-BCR is galectin-1 expressed by stromal
cells
- BCR signaling important for establishing allelic exclusion and initiating L chain
rearrangement
- Both require expression of membrane form IgM
Expression of functional heavy chain on the membrane inhibits what and initiates what?
- Correct Answer - Inhibits heavy chain rearrangement
- Transgenic mice with human IgM versus WT mice: showed that human heavy chain
IgM stops expression of mice IgM, making only human IgM
- Initiates L chain rearrangement despite no heavy chain rearrangement
- Need functional heavy chain expressed on surface of B cell for L chain rearrangement
(membrane IgM)
What does Allelic exclusion do and how does it occur? - Correct Answer - Allelic
exclusion guarantees that a B cell makes only one functional, non-self reactivity
antibody
- Synthesis of functional H chain turns off H chain rearrangement and turns on L chain
rearrangement
- Synthesis of functional L chain turns off gene rearrangement
- In mice: kappa light chains rearrange first, if both alleles are non-functional,
rearrangement of lambda light chain takes place, if both fail, then die
