B Cells and Antibodies of Adaptive Immunity Flashcards
What are the two main weapons of the adaptive immune system?
Antibodies and T cells
What is the main defense against extracellular bacteria?
Antibodies
Antibodies can also help protect against infection by viruses
What cells produce antibodies?
B cells
Where are B cells derived?
Like T cells, B cells are derived from common lymphoid progenitors in the bone marrow.
Where do B cells develop and mature?
Unlike T cells, B cells remain in the bone marrow throughout their development and maturation process.
What is the BCR?
The B cell receptor is a surface-bound immunoglobulin (mIg) with an associated Igα/Igβ component; antibodies are secreted immunoglobulin (sIg).
The BCR is responsible for antigen binding and determines the antigen specificity of the B cell.
What do B cells develop during maturation?
B cells begin to express the B cell receptor, BCR (also called membrane-bound immunoglobulin, mIg) as well as the Igα/Igβ co-stimulatory proteins.
What is the Igα/Igβ subunit responsible for?
Sending a signal to the inside of the cell once an antigen has been bound
(this is analogous to the CD3 complex on T cells)
What is clonal deletion?
Process of eliminating self-reactive B cells
During the developmental process, if the BCR of an immature B cells binds an antigen (usually a self-antigen) while still in the bone marrow, the Igα/Igβ co-stimulatory proteins sends a signal to the inside of the cell causing the cell to die.
(This is analogous to the negative selection that thymocytes undergo in the thymus.)
Discuss positive selection in regards to B cells.
As BCRs do not need to interact with processed proteins and MHC like the TCR of T cells, there is no similar process of positive selection.
What happens to B cells that complete the maturation process?
B cells that are not deleted develop into mature B cells that leave the bone marrow, circulate in the blood and migrate to the spleen and lymph nodes.
What is the the BCR of a mature, naïve B cell?
The BCR of a mature, naïve B cell is either membrane-bound immunoglobulin M (mIgM) or membrane-bound immunoglobulin D (mIgD).
Describe the structure of a BCR molecule, including the formation of its antigen binding pocket.
Each BCR molecule consists of 4 polypeptide chains: 2 identical heavy (H) chains and 2 identical light (L) chains.
Each of the immunoglobulin H and L chains has one V region (V = variable) and one C region (C = constant).
The VH (variable region of the Heavy chain) and VL (variable region of the Light chain) regions combine to form an antigen-binding pocket.
There are two antigen-binding sites per BCR (or immunoglobulin molecule).
How many antigen-binding sites are there per BCR molecule?
There are two antigen-binding sites per BCR (or immunoglobulin molecule).
What happens first in the expression of BCR?
The expression of the BCR first involves the rearrangement of immunoglobulin “gene segments” during development to form complete genes for the H chain and the L chain.
This process is covered in MICB 302.
How many BCRs will a single mature B cell have, and where?
A single mature B cell will have approximately 100,000 BCRs in its membrane.
How many epitopes will a single B cell bind?
All of the BCRs (i.e., both mIgM and mIgD) on a single B cell. Because the mIgM and mIgD have the same VH and VL regions, all of the BCRs will have the same antigen specificity.
Thus, a single B cell will bind only one or a few similar epitopes (antigenic determinants).
How do different B cells have different antigen specificity?
Different B cells will have different VH and VL regions in the BCRs (because they used different gene segments when constructing the gene for the H and L chains).
What are antibodies?
A set of proteins made and secreted by B lymphocytes.
They are also called immunoglobulins (Igs).
What do antibodies do?
Antibodies circulate in blood and other body fluids such as mucus.
Antibodies bind to macromolecules that are usually foreign to that individual.
What is immunity due to antibodies called?
humoral immunity (humors = fluids).
Describe antibody synthesis.
Antibodies are secreted proteins made by B cells.
The heavy (H) and light (L) chain mRNAs are translated into proteins by membrane-bound ribosomes.
The H and L chain polypeptides are translocated into the endoplasmic reticulum (ER) as they are synthesized.
In the ER, two H and two L chains are joined by di-sulfide bonds and assembled into a complete antibody molecule.
What is the main difference between membrane-bound immunoglobulin (mlgs) and secreted antibodies (slgs)?
Amino acid sequences at the carboxyl-terminus of the H chain.
For mIg, the amino acids are hydrophobic so that the polypeptide is anchored in the membrane when the vesicle fuses with the plasma membrane.
For sIg, the amino acids tend to be hydrophilic so that when the vesicles with the plasma membrane, the antibodies are released into the extracellular fluids.
Where can secreted antibodies be found?
Mainly in the blood, but are also found in bodily secretions such as mother’s milk, tears, saliva, gastrointestinal secretions, and the mucus secretions of the respiratory tract and the genitourinary tract.
What is another difference between membrane bound immunoglobulin (mlgs) and secreted antibodies (slgs)?
The polypeptides associated with the carboxyl-terminus of the H chain.
sIg does not associate with Igα/Igβ.
B cells secrete antibodies with the same specificity as their BCR.
What does it mean to say that each BCR is bivalent?
It has two antigen-binding sites.
The B cell receptor is made of one copy of the heavy chain and one copy of the light chain.
True or false?
False.
The heavy and light chains are joined by di-sulfide bonds and assembled into a complete antibody molecule in the endoplasmic reticulum.
True or false?
True.
The V regions of the heavy and light chains are involved in antigen recognition.
True or false?
True.
Cell surface immunoglobulins associate with the signalling proteins Igα and Igβ.
True or false?
True
Antibodies are insoluble proteins.
True or false?
False
The main difference between membrane-bound immunoglobulin (mIgs) and secreted antibodies (sIgs) is amino acid sequences at the amino-terminus of the heavy and light chains.
True or false?
False.
Immunoglobulin receptors exist on the surfaces of B cells but not on the surfaces of plasma cells or T lymphocytes.
True or false?
True
Both BCRs and TCRs have two antigen binding sites for each receptor.
True or false?
False.
B cells react with antigens through TCR antigen receptors.
True or false?
False.
There are secreted forms of both the BCR and TCR after the B cell and T cell (respectively) have been activated by antigen.
True or false?
False.
Where are immature B cells screened for self-reactivity?
Immature B cells that express a functional BCR are screened for self-reactivity in the bone marrow - those with high affinity BCRs are clonally deleted.
What happens to B cells that are not deleted?
B cells that are not deleted develop into mature B cells that leave the bone marrow, circulate in the blood and migrate to the lymph nodes and spleen.
What type of selection do developing B cells undergo?
Negative selection only.
The BCRs do not need to interact with MHC like the TCRs of T cells, so no positive selection is required
What is the point of B cell activation?
The whole point of B cell activation is to get the B cell to synthesize and secrete antibodies.
What determines the rolel of an antibody within the immune system?
the type of H chain that the antibody has
What is the signalling complex for TCR?
What is the signalling complex for BCR?
CD3
Igα/Igβ
What types of membrane bound immunoglobulin do mature, naïve B cells express?
IgM and IgD
They have the same VH and VL (therefore same antigen specificity) but different CH regions.
What is the difference between membrane bound immunoglobulin and secreted antibodies?
The difference between mIg and sIg is in the amino acids at the C-terminus of the H chain.
Also note sIg does not have the Igα/Igβ associated with it.
