(I) Lecture 8: B cell Immunity Part I Flashcards
B cells roles
- production of antibodies
- control of extracellular pathogens
Where are B cells developed?
In adult bone marrow
- bone marrow has many niches filled w/ hematopoietic cells
B cell development
During development, BCR genes in variable region are rearranged (DNA RECOMBINATION)
- why each B cell has a UNIQUE specificity against a unique antigen
NEGATIVE SELECTION: Those receptors who recognize self antigens get eliminated before leaving bone marrow
- so B cells don’t attack good cells
Naive B cells then enter circulation (with BOTH IgM and IgD)
Immature vs Mature B cell
immature B cell has only IgM
mature B cells has both IgD and IgM initially with the SAME SPECIFICITY
B cell activation
Contact w/ antigen in SLT activates B cells and leads to clonal expansion
Plasma cells
effector B cells
- make and secrete antibodies (IgM first)
- also make memory B cells
Antigen recognition
Shape and size of antigen determines specificity of recognition by antigen binding site of receptor
antibodies can recognize linear (exposed) or conformational determinants in folded proteins
BCR and antibody
BCR: membrane-bound form (surface of naive and memory B cells)
Antibody: secreted form (BCR secreted by plasma cells)
BOTH have the same antigen specificity
BOTH can bind pathogen/antigen directly (unlike TCR)
BOTH can bind to protein and non-protein antigens (unlike TCR)
Immunoglobulin classes
5 types
- IgM, IgD, IgG, IgE, IgA
Difference is in heavy chain CONSTANT REGION
Types of antigens that bind to BCRs
extracellular pathogens and toxins/allergens
Non-protein antigens
Multiple identical epitopes (ex. polysaccharides)
- B cells can bind but T cells cannot
- response does not involve T cells
NO long-term protection = NO high affinity antibodies
Locations of B-cell development and activation
Bone marrow
- generation of BCRs
- negative selection
SLT
- migration of B cells through circ system to lymphoid organs and B-cell activation
- antibody secretion + memory cells
B cell activation steps
Antigen recognition by follicular T cells induces signals that activate B cells
1. BCR binds to antigen
2. B cell and T cell bind (Co-stimulatory signaling)
3. Cytokine signaling
AFTER these 3 steps:
- clonal expansion: B-cell proliferates
- differentiation: plasma called, germinal centre B cells and memory B cells
activation happes in SLT
What happens if B cells don’t encounter its antigen? If they do?
If B cells do not encounter their antigen, it remains inactive and recirculates
If B cells bind its antigen it is activated
Where does B cell activation happen?
In the SLT
Germinal centre
- made up of rapidly dividing B-cells, follicular dendritic cells, T follicular cells (T cells are about 10%)
- largest 7-12 days after antigen stimulation
- where somatic hypermutation and class switching of antibodies happens
Where so somatic hypermutation and class switching of antibodies happen?
In germinal centres
How are germinal centres formed?
Activated B cells form germinal centres
- Naive B cells from bone marrow travel to lymph node and leave via efferent lymph
- If B cells encounter its antigen, they form a primary focus and start proliferating into a germinal centre
- Plasma cells generated during proliferation exit the lymph node
Does T cell or B cell immunity happen first?
T cell immunity happens first (T cells are needed for B cells to get activated
Paths of a naive B cell
If there are NO T cells, a naive B cell becomes a short-lived plasma cell w/ IgM
If there are T cells, a naive B cell enters the germinal centre (with Tfh) where it can differentiate to:
- long-lived class-switched plasma cell (w/ surface IgG or IgA) with improved affinity due to class switching and somatic hypermutations
OR
- long-lived memory B cell
First immunoglobulin molecule made
Mature B cells produce IgM first
Can produce other Ig classes via CLASS SWITCHING
Affinity maturation
B cells in the germinal centre can undergo somatic hypermutations in which the variable region of Ig genes are changed to improve affinity to specific antigen
Somatic hypermutation
Mutations in the heavy-chain and light-chain of VARIABLE region
IN germinal centre
improves affinity for antigen BUT does NOT change specificity
Class switch
Heavy-chain CONSTANT regions are replaced by the heavy-chain constant region of another isotype
Different cytokines will activate class switching for different Igs
