where do B cells under go negative selection?
in the bone marrow
where do B cells under go positive selection?
secondary lymphoid tissues
where are B cells activated?
in the peripheral lymphoid tissues (secondary LT)
what are the two types of effector B cells?
memory and plasma cell
once a B cell is a plasma cell can it revert back to a B cell?
what chemokine attracts B cells to the primary follicle?
what chemokine attract B B cells to the HEV?
CCL 21 and CCL19
where do B cells interact with FDCs?
in the primary follicle
what cells present antigen to B cells?
macs and FDCs
what does B cell activation drive?
what are follicular dendritic cells?
stromal cells involved in B cell development and activation
- accumulate antigens via complement receptors
- NO phagocytic activity NOT a classical DC
what is the receptor for bound complement to antigen on macs and FDCs
what are the three signals for B cell activation?
what two signals are requisite for B cell activation?
*without it the B cell becomes anergic
what does antibody crosslinking do?
what does co-receptor signaling do?
survival and proliferation
what are the two types of antigens a B cell can be activated by?
thymus dependent antigens
Tfh cell interaction required
expressed via MHC II
thymus independnt antigens
compliment bound antigen
lipids, carbs, toxins
Signal 1: antibody crosslinking
clustering and aggregation
Ig alpha and beta signaling
*does not tell B cell if the antigen is self or not, it just activates
Signal 2: B cell co-receptor signaling
**ensures target is pathogenic** prevents angery foreign or self antigen clonal expansion 1. B cell co-receptor complex (binds to complement) 2. PRRs 3. CD40
Signal 3: cytokine signaling
Tfh are most common source of cytokines, but local cytokines can provide signals if T cells are gone
four roles of cytokine signaling
survival and proliferation
what is a cognate pair?
when activated B and Tfh cells come together at the follicle boundary
*B cell is presenting the antigen via MHC II
how to Tfh cells aid in B cell activation
CD40 induces survival and proliferation (co-receptor signal)
- release cytokines
- induces differentiation and isotype switching
where do cognate pairs go first and what happens there?
- primary focus
- here the plasma cells just produce IgM to prevent systemic infection
- *no class-swithing or somatic hympermutation
After the cognate pair leaves the primary focus where do they go?
the secondary focus, which forms the germinal center
what happens at the secondary focus?
enormous proliferation to produce plasma and memory cells
- class switching and SMH
- selection of most specific plasma cells
what is a centroblast?
come after the congate pair gets to germinal center
- proliferating source of new B cells
- NO Igs on surface
- class switching
- create centrocytes
what is a centrocyte
- express surface Ig
- cannot class switch or SMH
- interact and selected for by FDCs
- programmed to die
what is class switching
RAG proteins reactivated in centroblast
change heavy chain
classes dictate effector function
what is somatic hypermutation
directed hypervariable region mutation single nucleotide insertions and subs produces new epitope binding region as centroblasts divide a mutation is introduced increases Ab affinity paired with selection process
what cell selects for high-affinity centrocytes?
*the Abs are required to compete to get the highest affinity Abs produced
what happens to FDC-bound centrocytes?
Tfh cells bind and give survival signal and further proliferation
-differentiation into plasma and memory B cells
what are the four broad effector functions for antibodies
Antibody-Dependent Cell-mediated cytotoxicity (ADCC)
why are Fc receptors important?
allow adaptive specificity to innate cells by binding to the antigen bound antibody
what are the functions of Fc receptors?
stimulate and inhibitor function -cytokine production/release -phagocytosis -degranulation -targeted killing involved in Ig transport IgG, IgE, IgA
what receptor transports IgG across membranes
what is poly-Ig receptor?
binds the the Fc portion of the dimeric IgA to transport to mucosal surfaces
what Igs generally neutralize?
IgA and IgG
what cells clear agglutinized antigens?
-they bind complement on antigens that are bound by Abs and deliver them to Macs which have Fc receptors and allow the agglutinized antigen to be killed
what are IgEs
cell surface receptors for mast, basophils, eosinophils
- targeted degranulation
- important in allergies
which two Abs initiate complement?
IgG and IgM
Antibodies provide passive immunity during development how?
IgG during gestation
IgA from breast milk
mother’s immunity passed to child