MIMG C185A Final Exam | Questions and Answers | 2025 Revised Update | 100% Correct -
UCLA.
What role does B cells play in? - -- Innate and adaptive immunity
--What are the 3 known subsets of B cells and what immunity do they play in? - -- 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? - -- 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? - -- 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 - -- 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? - -- 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? - --
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? - -- 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? - -- 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? - -- 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? - -- 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? - -- 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 - -
--What signal allows Pro-B cells to differentiate into immature B cells? - -- 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? - -- Antigen Independent
- Antigen Dependent
--What happens in the Antigen Independent stage? - -- 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? - -- 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? - -- 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? - -- 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? - -- 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? - -- 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? - -- 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? - -- 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? - -- 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? -
-- 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? - -- 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
--How does selection happen in the bone marrow? - -- Cells with non-productive IG gene
rearrangements and can't express functional Ig H or L chains are eliminated by apoptosis
- Immature B cells expressing surface IgM that reacts with self-antigens are eliminated by
apoptosis or change specificity (of BCR) to antibody by receptor editing
- Mature B cells that co-express IgM and IgD exit bone marrow for B cell differentiation
(small fraction)
--How does Negative Selection occur in the Bone marrow and what are two experimental
examples? - -- When immature B cells encoutner self-antigen within bone marrow, they are
eliinated either by apoptosis or receptor editing of BCR
- THERE IS DOMINANT EXPRESSION OF ALL MHC MOLECULES
UCLA.
What role does B cells play in? - -- Innate and adaptive immunity
--What are the 3 known subsets of B cells and what immunity do they play in? - -- 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? - -- 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? - -- 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 - -- 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? - -- 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? - --
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? - -- 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? - -- 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? - -- 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? - -- 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? - -- 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 - -
--What signal allows Pro-B cells to differentiate into immature B cells? - -- 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? - -- Antigen Independent
- Antigen Dependent
--What happens in the Antigen Independent stage? - -- 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? - -- 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? - -- 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? - -- 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? - -- 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? - -- 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? - -- 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? - -- 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? - -- 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? -
-- 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? - -- 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
--How does selection happen in the bone marrow? - -- Cells with non-productive IG gene
rearrangements and can't express functional Ig H or L chains are eliminated by apoptosis
- Immature B cells expressing surface IgM that reacts with self-antigens are eliminated by
apoptosis or change specificity (of BCR) to antibody by receptor editing
- Mature B cells that co-express IgM and IgD exit bone marrow for B cell differentiation
(small fraction)
--How does Negative Selection occur in the Bone marrow and what are two experimental
examples? - -- When immature B cells encoutner self-antigen within bone marrow, they are
eliinated either by apoptosis or receptor editing of BCR
- THERE IS DOMINANT EXPRESSION OF ALL MHC MOLECULES
