Lecture 14 (pt 1) Flashcards
where do B cells originate?
in the bone marrow
3 stages of B cells in BM
- pro-B cell
- pre-B cell
- immature B cell
what happens at each stage of B cells in BM?
at each stage BCR undergoes VDJ recombination
where do B cells go after BM?
Secondary lymphoid organs
describe dependence on antigen in BM vs secondary lymphoid organs
antigen independent in BM
antigen dependent in secondary lymphoid organs
3 subsets of B cells in periphery?
- follicular (B2) B cells
- marginal zone B cells
- B1 B cells
where are follicular B cells located?
in secondary lymphoid organs
where do follicular B cells originate?
BM
are follicular B cells T cell DEPENDENT or INDEPENDENT?
T cell dependent
what is the main function of marginal zone B cells?
generate Ab in the fastest way possible
are marginal zone B cells T cell DEPENDENT or INDEPENDENT? why?
T cell independent bc want to generate Ab as fast as possible
where are marginal zone B cells located?
secondary lymphoid organs
what proportion of B cells in the spleen are marginal zone B cells?
5% of B cells in spleen
describe role of B1 B cells relative to B2 and MZ B cells?
B1 B cells are between B2 and MZ B cells
where are B1 B cells located?
in pleural and peritoneal cavities and mucosa
why are B1 B cells unique?
they are self-renewing and arise from division of pre-existing B cells
role of B1 B cells
first-line response at mucosa to make neutralizing IgM
Describe type of antigen that activates T-dependent B cells
protein
How do T-dependent B cells make Ab?
requires activation by Th to make Ab
what type of B cells are produced in T-dependent response?
B2 B cells
2 types of antigens in T-independent response
TYPE 1 antigen = LPS, bacterial DNA
TYPE 2 antigen = highly repetitive surface structures (like flagellin)
How do T-independent B cells make Ab?
does not require activation by Th to make Ab
what type of B cells are made in T-indepedent?
B1 and MZ B cells
describe activation of B cells in T-independent response
antigen binds BCR which directly activates the B cell without T cell
in the T-independent response, describe the activation of B cells when there is HIGH CONCENTRATION OF TYPE 1 antigen
at high concentrations, the antigen is mitogenic bc it binds PRRs on B cell surface
in the T-independent response, describe the production of Ab when there is HIGH CONCENTRATION OF TYPE 1 antigen
produces polyclonal Ab with varying specificity
in the T-independent response, describe the activation of B cells when there is LOW CONCENTRATION OF TYPE 1 antigen
at low concentrations, B cells will ONLY activate if Ag binds thru Ig receptor
in the T-independent response, describe the production of Ab when there is LOW CONCENTRATION OF TYPE 1 antigen
only produces monoclonal Ab with 1 type of specificity
why does low concentration of type 1 antigen produce monoclonal antibody in T-independent response?
at low [Ag], B cells can only activate if they bind Ig receptor so the B cell only recognizes those with highest affinity so only makes B cell with 1 type of specificity
what determines whether T-independent is polyclonal or specific?
[Type 1 antigen)
example of type 2 antigen
capsular polysaccharide antigen
since the type 2 antigen is repeated on the pathogen surface, what does this lead to?
multiple BCR bind the antigen –> crosslinking which leads to B cell activation
what type of B cells does T-independent response to type 2 Ag activate?
MATURE B cells
who does not have the T-independent response?
children <5
why do children <5 not have the T-independent response?
T-independent response requires mature B cells and children <5 don’t have mature B cells
what Ab does the T-independent response make in response to Type 2 antigen?
IgM with LOW affinity
why does the T-independent response make low affinity IgM with Type 2 antigen?
There are no modifications (isotype switch, SHM, memory) that increase affinity
is there memory in T-independent response to Type 2 antigen?
no
why is there no memory in T-independent response to Type 2 antigen?
B cells don’t go thru germinal center (don’t need to be activated by T cells)
role of T-independent response to type 2 antigen
to quickly clear pathogen
2 signals in T-dependent response
- Ag binds and crosslinks Ig receptor
- Ag is processed and presented on MHC to be recognized by TCR on Th
what happens in the 2nd signal in addition to the p:MHC and TCR interaction?
CD40L on T cell interacts with CD40 on B cell
what does the 2nd signal in T-dependent response lead to?
allows T cell to secrete cytokines (IL-21) that can activate B cell
what happens if B cell does not receive signal from T cell?
B cell will be deleted or anergized
5 things that help from the Th cell leads to
- B cell expansion
- SHM
- Affinity maturation
- Isotype switching
- memory
what is required to make memory B cells?
Th cells!
how do the PREVNAR and Hib vaccines work?
both have repetitive polysaccharide structure on their surface to generate T-independent response
what is the issue with PREVNAR and Hib vaccines?
they don’t work in kids because they cannot induce T-independent response
how can you allow PREVNAR and Hib vaccines to work in kids?
use hapten-carrier where polysaccharide can be conjugated to a protein that will be recognized by a B cell –> both polysaccharide and protein will be presented to the T cell and allow production of Ab against polysaccharide
