Studied by 0 people
:(
What are the two primary lymphoid tissues?
Bone marrow, thymus
What is the function of primary lymphoid tissues?
Site of lymphocyte development (antigen-independent)
What is the function of secondary lymphoid tissues (aka periphery)?
Site of lymphocyte activation/differentiation (antigen-dependent)
What is the function of tertiary lymphoid tissues?
Chronic inflammation
What is lymphopoiesis?
Differentiation of lymphoid cells from a common progenitor
Where does lymphopoiesis occur for B cells?
Peripheral lymphoid organs
What are the parts of the bone marrow microenvironment?
Cellular compartment
Extracelluar matrix
Liquid compartment
Stromal cells
The bone marrow microenvironment provides cell-to-cell contact for developing B cells via adhesion molecules like __________ that bind ___________.
VCAM-1 and SCF; VLA-4 and kit
The bone marrow microenvironment produces which two cytokines?
IL-7 and CXCL12
What decides if a progenitor becomes a T-cell?
Notch signaling
What decides if a progenitor becomes a B-cell?
Early expression of IL-7R
Which CD protein is found on all hematopoietic stem cells?
CD34
Which CD protein is also known as IL-7Rα?
CD127
Which CD protein is present on all B cells?
CD19
What are the stages of B cell development?
Early pro-B cell
Late pro-B cell
Large pre-B cell
Checkpoint 1
Small pre-B cell
Checkpoint 2
Immature B cell
Mature B cell
What does checkpoint 1 check for?
If B cell expressed immunoglobulin heavy chain (IgH)
What does checkpoint 2 check for?
If B cell is self-reactive
What does a mature B cell express?
IgM and IgD
What is the order of chain rearrangement in BCRs?
Heavy chain then K light chain
In hematopoietic stem cells, which locus is closed but opens with commitment to B cell lineage?
Heavy chain
What do enhancers in BCR rearrangement flank?
Cμ and Sμ
In which phase of B cell is the DJ of heavy chain rearranged?
Pro-B cell
What happens if a cell fails checkpoint 1?
Try again with other chromosome
What happens if a cell fails checkpoint 1 twice?
Apoptosis
How efficient is rearrangement of the heavy-chain locus?
Not—50% of cells die
What happens if a cell passes checkpoint 1 on its first try and has an unused copy of a chromosome?
Allelic exclusion
Although the pre-B-cell receptor resembles the B-cell receptor, it differs by containing a surrogate light chain that is composed of what?
VpreB and λ5
What happens after a cell passes checkpoint 1?
Inhibit further heavy-chain rearrangement
Allelic exclusion
Proliferation of small pre-B cells
Begin K chain rearrangement
What is it called when a pre-BCR signals independent of ligand engagement?
Tonic signaling
Should B cells be able to recognize self-antigens?
NO
What is central tolerance?
Elimination of developing lymphocytes that are self-reactive in central lymphoid organs
What is peripheral tolerance?
Elimination of mature lymphocytes that are self-reactive in peripheral lymphoid organs
What is an immunologically privileged site?
Microenvironment where immune responses to allo- (foreign) and auto- (self) antigens are reduced
What are examples of immunologically privileged sites?
Uterus, eyes, brain, testes
What is positive selection of B cells?
Selection of non-self-reactive B cells
What happens to B cells that are positively selected?
Leave bone marrow
What are the three options for B cells in the bone marrow that are self-reactive?
Negative selection
Rescue attempt
Low affinity binding
What happens to cells that are negatively selected?
Apoptosis (clonal deletion)
How can a self-reactive BCR be rescued?
Receptor editing
B cells that can no longer be activated and are in a state of developmental arrest are called:
Anergic B cells
In anergic B cells, is there more IgD or IgM?
IgD
What are clonally ignorant B cells?
Weakly self-reactive B cells that fail to induce receptor editing, deletion, or anergy → become follicular or marginal zone B cells
What is a transitional B cell?
Gradual increase of IgD co-expression with IgM
What are the two types of cells that can exit the bone marrow?
Mature B cells and transitional B cells
How do mature B cells exit the bone marrow?
Express S1PR3 and follow S1P gradient to lymph node
When do transitional B cells that leave the bone marrow complete their maturation?
Enroute to the lymph node/spleen
What regulates co-expression of IgM and IgD?
Alternative splicing/RNA processing
When is IL-7R expressed during BCR gene rearrangement?
Early on
Successful signaling via BCRs starts even before heavy chain rearrangement and requires which two proteins?
CD79A/B (Igα/β) and Btk (Bruton's tyrosine kinase)
What inherited disease do mutations in Btk cause?
X-linked agammaglobulinemia
What disease is characterized by abnormally fast-growing B cells and aberrant rearrangement of the heavy and light chains?
Burkitt/non-Hodgkin lymphoma
What is the conventional B cell?
B-2
What is the B cell made during fetal development?
B-1
What are some fun facts about B-1 B cells?
Produce IgM
Low affinity binding
Polyspecific
Work against carbs and polysaccharides
Are B-1 cells more or less diverse than B-2 cells?
Less
Do B-1 cells require T-cells for activation?
No
Are B-1 cells self-renewing?
Yes
Where are follicular B cells mainly found?
Secondary lymphoid organs
Where are marginal zone B cells found?
Marginal zone of spleen
Which type of B cells provide the first line of defense against blood-borne pathogens?
Marginal zone
Which type of B cell is immunosuppressive?
Regulatory (Breg)
What is an activated B cell?
Plasma cell
What do naive B cells do?
Circulate the body until they encounter their specific antigen
What is the half-life of naive B cells?
1-2 months
How do naive B cells enter the lymph node?
High endothelial venules
Naive B cells that do not encounter their specific antigen require what to survive?
Survival signals from follicular DCs
Igα and Igβ combine with the surrogate light-chain components (VpreB and λ5) to form __________.
Pre-BCR
Igα and Igβ combine with the regular light-chain component (κ or λ) to form __________.
BCR
Igα and Igβ are made at which stages of B-cell development?
All
What happens to immature B cells whose B-cell receptors bind soluble monovalent self antigens?
Become anergic
Immature B cells have more IgM or IgD?
IgM
Mature B cells have more IgM or IgD?
IgD
Stromal cells are required for B-cell development as they support the B cells throughout their time in the bone marrow. The stroma promotes ___________.
Adhesion
Upon reaching what stage is a developing B cell irreversibly committed to the B-cell lineage?
Pro-B cell
Do heavy chains or light chains undergo receptor editing?
Light chains
What is the name given to the specialized cell type that helps to form the supporting framework required for B-cell development?
Stromal cell
Where do isotype switching, somatic hypermutation, and affinity maturation occur?
Germinal center
Which state of B cell has stopped rearrangement of the heavy chain genes but has not yet begun light chain rearrangement?
Large pre-B cell
What happens if the B-cell receptor of an immature B cell does not interact with multivalent self antigens present in the bone marrow?
The cell is exported to the peripheral circulation as an immature B cell
Which cell types express CD5?
B-1 and T cells
What is the name of the site where activated B cells undergo significant cell division?
Germinal center
The first checkpoint in B-cell development that tests the quality of the μ chain occurs at what stage?
Late pro-B cell
Maturation of B cells completes in the secondary lymphoid tissues in the __________________.
Primary lymphoid follicles
What does the pre-BCR consist of?
μ heavy chains + surrogate light chains
Whick chemokines attract B cells into the lymph node?
CCL19 and CCL21
Which chemokine attracts B cells into the primary lymphoid follicle?
CXCL13
Which is a type of B-cell tumor that arises from a germinal center B cell and does not express antigen receptor?
Hodgkin’s Lymphoma
