B Cells 1 Flashcards
describe the inactivation of T cells by Tregs
if a Treg recognizes p:MHC on an APC, the APC is presenting self-peptides
then Tregs will secrete cytokines that inhibit AUTOREACTIVE T cells which recognize self-peptides:MHC
what are the 3 signals of B cell activation?
signal 1: p:BCR
signal 2: TCR:pMHCII, CD40L:CD40
additional signal: cytokines from Tfh
what type of T cell activates B cells?
Tfh
where do antibodies exert their effects?
at the site of infection
what are the 3 roles of antibodies?
- pathogen neutralization
- opsonization
- complement activation
what cytokines does Tfh secrete for B cell activation?
- IL-21
- type 1 (INFgamma), type 2 (IL-4), type 3 (IL-17)
what do the type 1/type 2/type 3 cytokines cause?
activate B cells to produce specific types of antibodies
what is IgM?
antibody class that acts as a receptor on naive B cells
where do B cells arise?
in bone marrow
are B cells specific or non-specific?
specific
what does it mean for B cells to be clonotypic?
each B cell has specificity to a unique antigen, then undergoes clonal expansion once it meets the antigen
B cells are progenitors for which types of cells? (2)
- antibody-producing plasma cells
- plasmablasts
what are plasma cells? what is their function?
activated and differentiated B cells
they are the main antibody-secreting cells
where are plasmablasts located?
B cells in a lymph node
what are plasmablasts?
B cells before they are plasma cells, show some features of plasma cells but cannot secrete Ab
describe the location of BCR?
inactivated B cell: membrane-bound
activated B cell: secretes BCR as antibody
describe the general process of clonal selection and expansion
- stem cell undergoes gene rearrangement for unique specificity
- meets antigen, proliferation
- differentiation
- plasma cell can secrete antibodies
why can naive B cells easily reach the lymph node?
naive B cells circulating in the periphery regularly pass through the lymph nodes and spleen
how do naive B cells enter the lymph node?
through the HEV
what happens if a B cell doesn’t encounter an antigen in the lymph node?
leaves via EFFERENT lymphatics
what happens if a B cell doesn’t encounter an antigen after a few months?
dies via apoptosis
what happens if a B cell does encounter an antigen in the lymph node?
provides survival signal - SIGNAL 1
do B cells search for p:MHC?
no, B cells search for an antigen
what are the 3 ways that antigen can end up in the lymph node?
- Ag from pathogens arrive in lymph node via afferent lymphatics by chance
- Ag opsonized by complement proteins
- Ag transported via activated conventional DCs and transferred to follicular/residential DCs in lymph node
what type of cells become involved once opsonized antigens enter the lymph node?
subcapsular sinus macrophage (SCS macrophage)
what type of macrophages are subcapsular sinus macrophages?
resident macrophages
what do subcapsular sinus macrophages do?
they express complement receptor on their surface which binds the complement protein on the opsonized antigen, allowing the antigen to retain in the lymph node
why are subcapsular sinus macrophages different than normal macrophages?
they have low endocytic and degradative activity –> won’t phagocytose the antigen, will just retain the antigen on their surface
what do we mean by “antigen”
piece of a pathogen or the whole antigen
are all antigens bound to subcapsular sinus macrophages?
no, they can be free floating in the lymph node
what happens to the antigen bound to subcapsular sinus macrophages?
B cells can enter the lymph node and encounter the antigen, specifically binding the EPITOPE of an antigen via BCR
where can antigens in lymph node be transferred? what is this important for?
antigens can transferred onto surface of follicular dendritic cells –> this is important for later stages in B cell differentiation
describe the 2 potential parts of antigen binding to B cell
BCR binds antigen (sufficient by itself)
B cell expresses CD19 and CD21 co-receptors which bind complement (not necessary but can enhance signaling and activation)
what are the signaling subunits of BCR?
Ig-alpha and Ig-beta
describe the 2 steps of BCR signaling
- ITAM motifs on Ig-alpha and Ig-beta are phosphorylated
- multiple signaling pathways are activated
what is an extra way for signaling to occur that is not necessary but is helpful?
co-receptor complex with CD19 and CD21 binding complement proteins
what are the 3 main outcomes of BCR signaling?
- TFs activated, translocate, affect gene transcription
- survival signal via anti-apoptosis proteins
- cytoskeletal reorganization
what is the purpose of cytoskeletal reorganization?
endocytosis of BCR-antigen once signaling begins
describe the 3 steps of internalization and presentation of antigen by B cell
- antigen binds BCR, leads to signaling (exogenous)
- BCR-Ag complexes are internalized
- internalized Ag are processed and presented on MHC II
- this pMHC can interact with TCR on T cell
what are the names for the 2 types of signal 2
- Thymus-dependent antigens (TD antigens)
- Thymus-independent antigens (TI antigens)
which type of signal 2 is more common?
thymus-dependent antigens (TD antigens)
what provides signal 2 for thymus-dependent antigens?
activated CD4+ Tfh cell
what does signal 2 from thymus-dependent antigens lead to? (2)
- produces specific antibodies
- provides memory
what provides signal 2 for thymus-independent antigens (TI antigens)? how does this work?
TLR signaling
TLR on B cells binds PAMP with the same antigen as the B cell
what type of antigens are typically thymus-independent?
highly repetitive molecules that we are constantly exposed to, like LPS and crosslink on the BCR
do all B cells provide signal 2 for thymus-independent antigens?
no, only some B cells
does signal 2 from thymus-independent antigens cause antibodies or memory?
no
what are the 2 signals that occur during signal 2 of B cell activation?
- signal from pMHC that has bound to TCR and co-receptors on Tfh
- signal from CD40 on B cells bound to CD40L on Tfh
what does signal 2 directly result in?
- signaling
- activation of TFs
what does signal 2 lead to?
activation, proliferation, differentiation –> for antibody secretion
what is a common cytokine involved in B cell activation?
IL-21 from Tfh for B cell proliferation
what is the difference in the peptides that TCR and BCR recognize?
BCR recognize epitope on full antigen
TCR recognize small pieces of antigen on MHC of APC
what does linked recognition mean?
epitopes recognized by B cell and Tfh must be from the SAME ANTIGEN
but the actual peptide recognized by each may differ and recognition occurs differently for each cell type
what is the purpose of linked recognition?
once Tfh and B cell have each recognized their epitopes, the Tfh can effectively activate the B cell
