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081914 - TCR & Ig diversity, B cell dev, B cell/Ig
08/19/14, Stepkowski & Worth
46
Immunology
Graduate
08/22/2014

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Term
B CELL DEVELOPMENT
Definition
Stepkowski
Term
Broad stages of B cell development (4)
Definition
Production in bone marrow, negative selection against self-targeting B cells, foreign antigen activates B cells in secondary lymph tissues, activated B cells differentiate to antibody-secreting plasma cells and memory B cells
Term
Specific stages of B cell development (7)
Definition
Stem Cell, Early Pro-B, Late Pro-B, Large Pre-B, Small Pre-B, Immature B, Mature B
Term
H-chain rearrangement occurs in which stages
Definition
Heavy chain has VDJ segments. Early Pro-B: D-J rearrangement. Late Pro-B: V-DJ Rearrangement. Large Pre-B: Rearrangement complete, first functional heavy chain
Term
L-chain arrangement occurs in which stages
Definition
Light chain has VJ segments only. Small Pre-B: V-J rearrangement. Immature B: VJ Rearrangment complete, first functional light chain.
Term
Ig status of mature B cell
Definition
IgM and IgD on surface
Term
Ig status of immature B cell
Definition
IgM on surface
Term
Ig status of small pre-b cell:
Definition
µ chain in endoplasmic reticulum
Term
Ig status of large pre-b cell:
Definition
µ heavy chain, surrogate light chain, pre-b receptor on cell surface
Term
Ig status before Large Pre-B cell stage:
Definition
None
Term
Role of stromal cells in bone marrow for B cell development
Definition
1) provide cell-cell contact with developing B cells, and 2) provide growth factors including Stem Cell Factor (SCF) and IL-7
Term
Role of Stem Cell Factor produced by stromal cells
Definition
Promotes pro-B cells
Term
Role of IL-7 produced by stromal cells
Definition
Induces proliferation and development of pre-B cells
Term
Regulators of B cell development: RAG-1 and RAG-2
Definition
Make double strand breaks for rearrangement, recognizing heptamer/nonamer sequences
Term
Regulators of B cell development: Bruton's tyrosine kinase (Btk)
Definition
On X chromosome, essential for B cell maturation. Mutation leads to B cell deficiency: X-linked agammaglobulinemia - no mature B cells
Term
Regulators of B cell development: TdT
Definition
Terminal deoxynucleotidyl transferase - adds random nucleotides to cut ends of DNA, important for junctional diversity. On in pro-B, off in pre-B
Term
Regulators of B cell development: c-Kit
Definition
Growth factor receptor active from stem cell to Late Pro-B stage
Term
Regulators of B cell development: IL-7 Receptor
Definition
Growth factor receptor active from stem cell to Small Pre-B Stage
Term
Five types of immunoglobulin classes
Definition
Ig: M, D, G, A, E
Term
Ig classes that are monomer
Definition
G, D, E
Term
Ig classes that are pentamer
Definition
M
Term
Ig classes that are dimer
Definition
A
Term
X-linked agammaglobulinemia
Definition
Condition where all Igs are missing; discover via immunoelectrophoresis
Term
Swollen lymph nodes are due to
Definition
Highly proliferative B cells in lymph node germinal centers
Term
B cell activation - 3 signals
Definition
1) antigen binding/internalization, 2) CD40L from TH2 helper cell interacts with CD40 on B cell, 3) cytokine environment stimulates proliferation and isotype switching
Term
Fate of B cells after activation (2)
Definition
1) mature into plasma cell, 2) mature into memory B cell
Term
Plasma cell characteristics
Definition
Extensive ER, highly antibody-producing
Term
Thymus Independent Antigen (TI-1/TI-2)
Definition
Bacterial products that can activate B cells without T help
Term
TI-1: Which cells respond? What mode?
Definition
All B cells; polyclonal. Completely antigen-independent response (lipopolysaccharides produced by bacteria trigger toll-like receptor 4, causing activation)
Term
TI-2: Which cells respond? What mode?
Definition
Mature B cells; because they cause proliferation via crosslinking. Still an antigen-specific response (bacteria binding to B cell receptors triggers)
Term
Antibody Function
Definition
Bind and neutralize toxins
Term
Ab:Ag Valence
Definition
# of antibodies an antigen can bind at one time
Term
IgM: structure, function
Definition
Pentamer, activates complement, 1st formed in response to an antigen
Term
IgM: Location
Definition
Blood, and around critical organs like heart
Term
IgD: structure, function
Definition
Monomer, stays membrane bound, shuts down B cells after antigen binding, 2nd type formed in response to an antigen
Term
IgA: structure, function, types
Definition
Dimeric, associated with secretory surfaces. Secretory and monomeric forms
Term
Secretory IgA: receptor
Definition
Polymeric Ig receptor
Term
Secretory IgA: location
Definition
all mucosal surfaces; the only one in breast milk
Term
Monomeric IgA: receptor
Definition
Fc alpha receptors on leukocytes; this triggers burst of oxidizing agents to kill
Term
Monomeric IgA: location
Definition
All
Term
IgE: structure, function
Definition
Monomer, in blood, associates with mast cells in tissue, basophils in blood, to trigger immune response via Fc epsilon receptor. Can assist eosinophils in attacking large parasitic worms
Term
IgG: structure, function
Definition
Monomer, induces complement fixation, Highest concentration Ig in an immune response
Term
Fc gamma receptor, and IgG: Activating types:
Definition
Fc gamma receptor I, IIA/C, IIIA/B. These activate phagocytosis and oxidizing agent burst.
Term
Fc gamma receptor, and IgG: Inhibitory types:
Definition
Fc gamma receptor IIB1, 2. May shut down B cell from producing antibody in B cells, macrophages, neutrophils
Term
IgG: location
Definition
Everywhere except brain; chief Ig type in fetus
Term
Neonatal immunity: FcRn
Definition
Neonatal Fc receptor, sequesters excess IgG in vascular endothelial cells, will release if concentration drops
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