What role does B cells play in? correct answers - Innate and adaptive immunity
What are the 3 known subsets of B cells and what immunity do they play in? correct answers -
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 answers - 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 answers - 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 answers - 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 answers -
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
answers - 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 answers - 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 answers - 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 answers -
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 answers - 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 answers - 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 answers
, What signal allows Pro-B cells to differentiate into immature B cells? correct answers - 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 answers - Antigen Independent
- Antigen Dependent
What happens in the Antigen Independent stage? correct answers - 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 answers - 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