B Lymphocyte Ag Recognition Flashcards
What type of antigens can BCR recognize?
Proteins, polysaccharides, lipids, and nucleic acids
Do BCR’s have more or less diversity than TCRs?
Less
Which region of the BCR confers isotope and effector function?
Constant region- can also switch immunoglobulin from membrane bound to soluble
What happens to the specificity of B cells upon antigen binding?
Highly increased (but baseline BCR specificity is still higher than TCR)
What is the on and off rates of BCRs?
Rapid on-rate and variable off-rate
What is the complementarity determining region of BCRs?
Hypervariable area recognizing and contacting antigens
What is the structure and general function of IgA?
Dimer. Mucosal immunity
What is the structure and general function of IgE?
Monomer. Mast cell activator
What is the structure and general function of IgG?
Monomer. Fc dependent phagocytosis, placental transfer, opsonizer, complement system.
What is the structure and general function of IgM
Pentamer. Naive B cell antigen receptor and complement activation. Primary response**
What happens to IgG expressing B cells after activation?
Isotype switching and IgG release
What happens to high-affinity Ig expressing B cells following activation and differentiation?
affinity maturation= B cell makes Ab for repeated exposure (memory b cells)
When do B cell precursors rearrange their immunoglobulin genes?
After contact with bone marrow stromal cells
What is baseline variability in B and T cells?
Multiple V region genes (RAG1/RAG2)
What is combinatorial variability in B and T cells?
VDJ joining (limited by number of VDJ combinations)
What is junctional variability?
Inaccurate gene segment splicing for unlimited diversity.
What are the three types of junctional variability?
- exonuclease removal of nucleotides from V,D,J regions.
- terminal deoxyribonucleotidyl transferase (tdt) adds in nucleotides between V&D and D&J regions to form N regions.
- DNA addition before DNA break repair to form P regions.
What is second combinatorial variability in B and T cells?
H&L chain random assortment
What is somatic hypermutation?
High frequency point mutations in IgG heavy chain and light chain in germinal B centers.
What types of cells undergo somatic hypermutation?
B cells only!
What is the outcome of somatic hypermutation?
Increases affinity of antibody for antigen and increases selective survival of that B cell for affinity maturation
Which enzymes take part in somatic hypermutation?
Activation-induced cytidine deaminase and APE1 (not in humans)
What is heavy and light chain substitution?
Pre-BCR undergoes heavy and light chain mRNA splicing to form IgM and IgD intermediates for positive and negative selection
What are lambda-5 and VpreB?
surrogate light chain components for B cell receptor chain substitution during devo
What is the function of FLT3/FLT3R?
Binding of FLT3R on FLT3 on BM stromal cell induces IL-7R expression (IL-7 = lymphocyte growth)
What is the function of stem cell factor in early B-cell development?
SCF on bone marrow stromal cell binds receptor kinase c-KIT for pro B cell proliferation
What is the function of CXCL 12?
Stromal cell-derived factor, SDF-1 involved in CNS development
What are the general steps to the germinal cell reaction?
- B cell activation by Ag & helper T cells (CD40L + cytokines)
- Migration of B cell into germinal center
- B cell somatic mutation with varying affinities for antigen
- B cells with high affinity membrane Ig bind FDCs and present to T cells
- Binding to FDCs/ T cell interaction further activates the B cell and those cells survive.
- Cells that don’t bind die
- Germinal center proliferation of surviving B cells
What is unique about the B cell germinal center reaction?
B cells can display the antigens on their own MHC II receptors (but usu presented to by DCs)
What are the steps to B lymphocyte activation?
- Complement activation= C3d binds microbe
- Ag binds BCR and complement binds CD19/CR2 or Ig-alpha/beta
- Be cell activation via CD19 or Ig-alpha/beta signals
Does the BCR have a signaling component?
NO uses CD19 or Ig-alpha/ beta
Which immunoglobulin is present most during the initial reaction and which upon repeated exposure?
IgM= initial exposure IgG= repeated
Which signaling molecule determines the IgM isotope?
No signal, IgM = default
Which signaling molecule determines the IgG isotope?
IFN-gamma
Which signaling molecule determines the IgE isotope?
IL-4
Which signaling molecules determine the IgA isotope?
cytokines produced in mucosal tissue (TGF-beta, BAFF)
What is Omenn syndrome?
RAGnull mutation= no B cells in skin. Txt= BMT
What is SCID?
Defects in DNA repair = low Ig and TCR diversity. Tx= BMT
What is ataxia telangiectasia?
ATM null mutation= low B cells. Txt= Ab, vaccines, IVIG
What is AID deficiency?
low Ab diversity due to lack of class switching and hypermutation = high IgM numbers. Txt= IVIG
Describe thymus dependent Ab responses
Usually for protein Ag= IgM and subclass switching for affinity maturation and second response generation
Describe thymus-independent Ab responses
Polysaccharides, glycoproteins, and nucleic acid antigens. IgM generated but no affinity maturation and limited secondary response.
What are the two B cell types found in the spleen and other lymphoid organs?
Follicular B cells (B2) and marginal zone B cells
What is the function of follicular B cells (B2)?
Isotype-switched plasma cells that generate high-affinity antibodies against proteins
What is the function of marginal zone B cells?
Recognize lipids, polysaccharides and generate mainly short-lived plasma cells and IgM
What type of B cells are found in mucosal tissue and what is their function?
B1 cells- recognize lipids and polysaccharides. Produce mainly IgM and are short-lived plasma cells
How is the BCR signal terminated?
Ab/Ag binds B cell IgG receptor and Fc receptor. Fc receptor contains ITIMS that inhibit the ITAMS
