Lecture 14 (pt 1) Flashcards by Zara Jalil

where do B cells originate?

in the bone marrow

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3 stages of B cells in BM

pro-B cell
pre-B cell
immature B cell

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what happens at each stage of B cells in BM?

at each stage BCR undergoes VDJ recombination

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where do B cells go after BM?

Secondary lymphoid organs

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describe dependence on antigen in BM vs secondary lymphoid organs

antigen independent in BM

antigen dependent in secondary lymphoid organs

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3 subsets of B cells in periphery?

follicular (B2) B cells
marginal zone B cells
B1 B cells

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where are follicular B cells located?

in secondary lymphoid organs

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where do follicular B cells originate?

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are follicular B cells T cell DEPENDENT or INDEPENDENT?

T cell dependent

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what is the main function of marginal zone B cells?

generate Ab in the fastest way possible

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are marginal zone B cells T cell DEPENDENT or INDEPENDENT? why?

T cell independent bc want to generate Ab as fast as possible

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where are marginal zone B cells located?

secondary lymphoid organs

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what proportion of B cells in the spleen are marginal zone B cells?

5% of B cells in spleen

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describe role of B1 B cells relative to B2 and MZ B cells?

B1 B cells are between B2 and MZ B cells

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where are B1 B cells located?

in pleural and peritoneal cavities and mucosa

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why are B1 B cells unique?

they are self-renewing and arise from division of pre-existing B cells

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role of B1 B cells

first-line response at mucosa to make neutralizing IgM

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Describe type of antigen that activates T-dependent B cells

protein

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How do T-dependent B cells make Ab?

requires activation by Th to make Ab

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what type of B cells are produced in T-dependent response?

B2 B cells

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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?

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

1. Ag binds and crosslinks Ig receptor 2. 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

1. B cell expansion 2. SHM 3. Affinity maturation 4. Isotype switching 5. 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