6- Development of B cells Flashcards
Where do B cells develop?
Bone marrow
What do the B cells acquire during the first stage of B cell development?
Functional Ag receptors
Why is the second stage of B cell develolpment called “negative selection?”
Because it gets rid of B cells that react to the bodys own tissues
What occurs during the 3rd (positive selection) stage of B cell development?
Immature B cells compete for the limited # of sites in the follicles of the secondary lymphatic tissues.
Where do the B cells go in the fourth stage of B cell development?
The mature B cells travel in the blood and lymph looking for infection.
What occurs when an Ag binds to the BCR during the 5th stage of B cell development?
It leads to proliferation and clonal expansion of The Ag-specific B cell.
What do B cells morph into during the 6th stage of B cell development?
Plasma cells
What is the fxn of plasma cells?
They provide Ab’s that attack ongoing infection and create memory B cells for the quick killing of future infections.
What occurs when the B cell is a “pro B cell?”
Rearrangement of the heavy genes
What type of markers are identifiable in pro-B cells?
TdT, MHC-II, CD19, CD20, CD, 21, and CD40.
What is the first type of heavy chain produced in the “pre-B cell?”
μ heavy chain
What occurs when the B cell is a pre-B cell?
Rearrangement of the light chains.
What is expressed on the cell surface of immature B cells?
IgM (μ chains + light chains) + Igα & Igβ polypeptides
Which Ab is expressed on the cell surface on mature B cells?
IgD
Clinical Q: An analysis of B cells during development reveal cytoplasmic μ+. Which stage of B cell development are the B cells in?
Pre-B cells
Clinical Q: An analysis of B cells during development reveal surface IgD. Which stage of B cell development are the B cells in?
Mature B cell
Clinical Q: An analysis of B cells during development reveal no surface or cytoplasmic markers other than the normal CD20, TdT and MHC-II. Which stage of B cell development are the B cells in?
Pro-B cell
Clinical Q: An analysis of B cells during development reveal surface IgM and it’s the only Ab on the surface. Which stage of B cell development are the B cells in?
Immature B cell
Which Ab’s do memory cells have on their surface?
IgG, IgA, or IgE
What is the fxn of stromal cells in B cell development?
They both make specific contacts with developing B cells and produce growth factors for the B cell.
What is the function of the surrogate light chain?
It mimics an Ig light chain and forms the pre-BCR
What happens if the μ chain assembles poorly with the surrogate light chain?
A functional BCR isn’t make and the cell dies by apoptosis
What is the fxn of Btk (brutons tyrosine kinase)?
It’s involved with signal transduction and B cell development beyond the pre-B cell stage.
What are λ5 & VpreB’s?
They are pre-BCR’s
What are the functions of Igα & Igβ?
They form pre-BCR’s and BCR’s
When are Igα &Igβ turned off?
When Ag-stimulated B cells differentiate into plasma cells.
What is missing in an agammaglobulinemia patient?
Btk gene
What is the clinical basis for agammaglobulinemia symptoms?
No Btk –> no circulating Ab’s –> recurrent infections
What is the main fxn of CD5 B-1 cells?
They are weird B cells that make Ab’s against common bacterial polysaccharides.
What type of disease is caused from B-1 cells that develop postnatally?
Chronic lymphocytic leukemia (CLL)
What stage of B cell development does B cell selection occur?
Immature B cells
What is the purpose of B cell selection?
Get rid of B cells that react to self-Ag’s and keep those which express IgM and IgD for pathogenic Ag’s
What happens to an immature B cell if it binds to self-Ag’s?
it’s signaled to continue light chain gene rearrangement or to die by apoptosis.
Which chemokine attracts immature B cells in the blood to the HEV?
CCL21
Which chemokines attract the B cells into the lymph node?
CCL21 and CCL19
Which chemokine, secreted from folicular dendritic cells, attracts B cells into the primary follicle?
CXCL13
What happens when immature B cells enter the follicle?
They interact with protein on FDC’s that signal their final maturation into a mature B cell. yay.
Where in the lymph nodes do B cells mature to plasma cells?
Germinal centers
What causes a B cell to differentiate into a plasma cell?
Activation by CD4 T cells.
What type of Ab’s do plasma cells secrete?
IgM
What is the job of the plasma cell?
They’re a memory cell that continuously synthesizes and secretes an Ab for an Ag that the body once encountered.
Which stages of B cell development are “antigen independent?”
Stem cell –> pro-B –> pre-B –> Immature B –> mature B
What are the “antigen dependent” stages of B cell development?
Mature B cell –> plasma cell or memory cell
What are naive B cells?
They’re mature B cells that left the bone marrow but have not yet encountered its specific Ag
What are memory cells?
They’re Ag-specific B cells that are produced from activated B cells during a primary infection
What causes memory cells to differentiate into plasma cells?
Subsequent exposure to their specific Ag