B Cell Development/Activation/Fx Flashcards
Types of epitopes
Mitogen
Chemical that induces cells to undergo mitosis - certain mitogens can trigger lymphocyte DNA replication and division in an antigen-independent manner
Hapten
Small, organic molecule that is foreign but too small to induce and adaptive immune response unless it is bound to a larger (typically protein) antigen
What portion of the Ab determines its class?
There are five different heavy chain constant regions, which dtermine the five different Ab classes
Complementarity determining regions (CDRs)
Abs
aka Hypervariable regions
Each heavy and light chain contains 3 sub-regions that strongly impact Ab/Ag binding affinities (but not ID of Ag)
Ig domains
Repetitive looped domains created by intra-chain disulfide bonds
IgD
Marker for naive, mature B cells - necessary for naive B cell activation
IgA
Monmer in serum and dimer in secretions
Dimer - two IgA molecules joined by a J chain
Mucosal immunity
B cell development before antigen contact
RAG deficiency
Cause of SCID - characterized by lack of T/B cell function
Inability to successfully recombine the TCR/BCR genes causing developing lymphocytes to undergo apoptosis
Pt’s present w/ failure to thrive, absent thymic shadow on CXR, and repeated severe bacterial/viral/ any other infections early in life
Bone marrow stromal cells in B cell development
Provide cell adhesion molecules (CAMs) and cytokines (i.e. IL-7) to nurture B cell development
Stromal cells also present Ag during negative selection
What process simultaneously produces IgM and IgD in a mature, naive B cell
Alternative splicing
Which BCR gene is rearranged first?
The heavy chain gene
What initiates immunoglobulin light chain gene rearrangement?
A functional μ (IgM) heavy chain protein
What type of selection do immature B cell clones undergo in the bone marrow?
Negative selection - if they react w/ self-Ags = apoptosis
When do immature B cells exit the bone marrow
After surviving negative selection - enter circulation and then secondary lymphoid tissue primary lymphoid follicles
What causes B cells to develop into mature B cells?
Interacting with DCs in a primary lymphoid follicle - DCs secrete cytokines that drive B cells to maturity
Alternative splicing of the H chain mRNA in mature, naive B cells
Does not change Ag-binding affinity or Ag specificity - it just allows the cell to express IgD and IgM versions of the BCR at the same time
X-linked Bruton’s Agammagolbulinemia
Primary immunodeficiency that results from defects in the B cell-specific, Bruton’s tyrosine kinase (BTk) that is express early in B cell development
B cells fail to mature beyond the pre-B stage
Infants are usually well for first six months of life - subsequently develop recurrent infections - particularly w/ encapsulated bacterial and mucosal pathogens**
Circulating B cells and all Ig classes are absent
T cell development is unaffected
Summarize B cell development
- Stem cell in bone marrow
- Successful rearrangement of μ heavy chain gene
- Successful rearrangement of κ or λ light chain gene & production of surface IgM BCR
- Negative selection in bone marrow
- Continuing development in primary lymphoid follicle
- Alternative splicing to make IgM and IgD
- Mature B cell
Where does B cell activation occur?
In secondary lymphoid tissues (typically the follicle)
T-cell dependent B cell activation signals
- BCR crosslinking by specific Ag plus BCR co-receptor complex (CD19, 21, and 81) activation - stimulates endocytosis of the BCR-bound antigen, B cell Ag presentation, and B cell migration to the T cell zone in secondary lymhpoid tissue
- CD4+ Th2 cells provide help through cytokines and direct physical interactions to drive B cell proliferation and differentiation
After antigen-mediated activation of a mature B cell - alternative splicing to produce IgD is turned off
Plasmablasts
Secrete low affinity IgM - do not undergo affinity maturation
Opsonization
Coating surface of extracellular path w/ IgG/C3b
Require Fcγ receptors on phagocyte surface (IgG)
or CR1 receptors (C3b)
