14: B cell activation and Ab production I Flashcards
how do B cells develop
from bone marrow precursors in the absence of ag
how are humoral immune responses activated
recognition of Ags by BCR
what do Ag do to B cells
activate naive by binding membrane IgM and IgD
structure of IgM
pentamere w/ 5 subunits
how many Abs can be produced from a single B cell
5000 Abs cells per week
what is the peak humoral immune response per day
10^12 Abs
what causes the proliferation of activated B cells
Ags, T helper cells and other stimuli
what can a clonal B cell become
plasma cell, or other IG isotype or may undergo affinity maturation or memory cells
what is also activated with B cells by Ag binding
more costimulatory molecules produced
how does B cell proliferation happen in relation to T cell
downstream of it by CD 40L
what causes isotype switching
intracellular pathogen
what do plasma cells do
secrete antibodies
what B cells become memory or have affinity maturation
High affinity Ig expressing B cells
primary antibody infection starts with
short lived plasma B in LO, more IgM than Ig G then low level Ab production and long lived plasma cells in bone marrow f
secondary antibody respones
Memory B then Plasma for more IgG and long lived plasma cells in bone marrow and Memory B cell levels increase
what happens to naive B cells in primary immune response
stimulated by Ag to activate and be Ab secreting for more IgM than IgG
secondary immune response on B cells
same Ag stimulates memory B cells for more IgG than IgM
which is difference btwn secondary and primary immune response
secondary produces more Abs faster
what part changes for isotype switching
heavy chain
what is induced by Ag Ab binding
affinity maturation
what immune response has affinity maturation
secondary
primary is induced by what Ags
any type
what Ags produce secondary immune response
mainly proteins
follicular B cells respond to and initiate what
protein Ags for T dependent Ab resonse for helper T cells
what is another name for follicular B cells
B 2 cells
which B cell produces long-lived plasma cells
B2 or F B cells
waht do Marginal B cells respond to and initiate
multivalent Ags for T independent
what do B1 cells respond to and induce
multivalent Ags at mucosal sites and are T independent
what is another name for MZ B cells
B2 cells
what Ig is produced by MZ and B1 cells
IgM
usual target of B1 cells
carbohydrates
memory B cells usually come from
B2 cells
where are B2 cells usually
throughout body
how are B2 cells replaced
continually by bone marrow in adult life
where do B1 cells come from
fetal liver during the 8th week of gestation
what do B1 cells represent
transitional type of lymphocyte to bridge innate and adaptive
problem with B1 cells
not very diverse and limited compared to B2 cells
what are B1 Abs directed against
conserved microbial Ags
transport of Ags to B cells
have to be captured and taken to B cells in lymphoid organs
where are B cells located at in Lymphoid organs
follicles
other names for follicular B cells
recirculating or B2 Cells
how do F B cells recirculate
from one to another secondary lymphoid organ
secondary lymphoid organs
spleen, lymph nodes and mucosal lymphoid tissue
follicles are in what
secondary lymphoid organs
what guides the movement of B cells
CXCL13 chemokine
where does CXCL13 come from
Follicular DCs
what is not expressed by FDCS
MHC Class II
what can an FDC not do
phagocytose and process Ags for Class I MHC
what immune response to FDCs help in
adaptive immunity
what else is guided by CXCL13 besides B cells
TFH cells
how long can an FDC have an immune complex on its surface
weeks to months
what mediates Ag retention by FDCs
FcyRIIb Fc receptor as well as CR1, CR2 (CD 21) complement receptors
what do the immune complexes of FDCs drive
antibody affinity maturation
what plays a role in germinal center reactions
FDC receptors
how are Ags presented to B cells
in intact native conformation and not processed by APCS
how are small B cells delivered to follicles
afferent lymphatics and conduits
how are large Ags delivered to B cells
subcapsular sinus macrophages or DCs in medulla
how do afferent lymphatics drain in LN
into the subcapsular sinus of the LNs
soluble Ags properties and how they reach B cells in LN
smaller than 70 kD and get to follicles for direct interaction
transport of large Ags in LN
captured by resident FDCs and transported to activated B cells in follicles
how are microbes and Ag-Ab complexes taken to B cells in LN
captured by subcapsular sinus macrophages and deliver Ags to follicles
where are T cells located in marginal zones
periarteriolar lymphoid sheaths (PALS)
distinctive cell types in marginal zones
MZ macrophages and marginal B cells
what is the marginal zone
barrier between red pulp and white pulp of spleen
which part of the spleen houses lymphocytes
white pulp
how do lymphocytes and DC enter the white pulp
marginal sinus between marginal zone and white pulp
how do Ag in immune complexes bind B cells
CR2 complement receptors on MZ B cells
what is the role of MZ B cells with immune complex Ags
transfer to follicular DCs
how are blood borne pathogens handled
captured by pDCs and transported to spleen for MZ B cells
what in spleen captures polysaccharide Ag
MZ macrophages to give to MZ B cells
how are MZ B cells independent of BCRs
bind complexes with AG and coat in CR complement fragments to shuffle them to follicular region
where do FDCs express high levels of CR
follicles to compete for binding to Ags presented by MZ B cells
what happens after CR on FDC binds Ag
MZ B cells go back to MZ
what are MZ B cells to B2 follicular cells
shuttle for Ags
when is a T dependent response required
protein Ags for help of CD4+ T helper cells
which T cells help B cells and how
TFH leads to the formation of germinal centers to activate B cell proliferation
which Ags use T indepentent
multivalent Ags such as polysaccharides, lipids, and nucleic acids
how do TI responses work
BCR binding and potentiated signals from other receptors on B cells
what potentiates B cell activation
CR2 and TLRs
role of CR 2(CD21) on BCR
binds C3d on microbe while Ag bind BCR as a co-receptor
microbe bound by CR2 is coated in
complement
how is complement activated in B cell response
non-microbial polysaccharides or microbe itself.
2nd form to cause B cell activation
PAMP recognition by TLRs at same time as Ag binding to BCR
what does F B cell survival depend on
signals from BCR and inputs from BAFF
how does BAFF work
provides maturation and survival signals through its receptor
what produced BAFF
myeloid cells in lymphoid follicles and bone marrow
parts of BCR signaling for activation
BCR binding initiates then internalizes bound Ag into endosomal vesicles
how is protein Ag presented to
processed and presented as MHC II on B cell surface for TH cell to recognize
what happens after TH cells recognize MHC II peptide complexes
stimulate B cell response
what response is B cell presenting to T cell
hapten carrier conjugates
what on BC helps TH recognize Ag and activate it
CD40 that binds CD40L on THC
what does activate THC in TCD response cause
activated B cells for proliferation
what does BT interaction lead to
isotype switching and shortlived plasma cells
what are germinal centers for
B cells mutate, affinity maturation, ISOT switch, memory cells and long lived plasma cells
extrafollicular B cell response goes where
medullary cords of LN and junction between TC zone and red pulp of spleen
what are the two B cell T dependent responses
Extrafollicular and Follicular/Germinal centers
which B cell T dependnent response has more everything
Follicular
what must happen for TfH cells to activate B cells
activation of T cells by DCs then by activated B cells to go to Germinal centers to activate more B cells
which cytokine helps develop GC B cells and plasma cells
IL 21
what controls isotype switcing from TFH cells
IFNy and IL4
when are TFH cells made from activated T cells
4-7 days after Ag exposure
what to TFH cells express
inducible costimulators, PD1, IL 21, Bcl-6
what do Dark zones in follicles mean
center of GC where B cells are proliferating
what happens to B cells in germinal centers dark zone
extensive isotype switching and somatic hypermutation of IgV gene
what happens in light zones of GC
encounter FDCs with Ags and TFH cells
which B cells survive and what do they become
highest affinity Ig receptors and become Ab secreting and memory B cells
where to Ab secreting B cells go
bone marrow as long lived plasma cells
where do memory B cells go
recirculating lymphocyte pools
stains dark zones of GCs
antiKi67 Ab
stains light zones of GCs
anti CD 23 on FDCs
what causes activated B cells to go to T cell zones
CCR7
