B cell activation (bowden 9/5) Flashcards
Clonal selection
The process of gene rearrangement of the heavy and light chains and the combinatorial association of these chains occurs during B cell development and is independent of antigen.
antigen simply selects those clones which have the appropriate receptor
the selected clones are then activated, proliferate, and differentiate into antibody secreting plasma cells
IL-3
acts on immature progenitors
CD20 and CD19
on surface of mature B cell
these are pan B cell markers
if you do an analysis of someones lymphocytes in their blood, use antibodies against CD20 or CD19 to look for those
Mature naive B cells exit marrow and enter what?
secondary lymphoid organs…
Lymph nodes and spleen
enter via HEV
if not activated by antigen they die
what do B cells that develop from fetal liver-derived stem cells differentiate into?
B-1 cells
these response to non-protein Ag in the mucosa
found in GALT/MALT/BALT
have an extra marker on their surface (CD5+)
make predominantly shortlived IgM responses
what do B cells that develop from BM progenitors after birth differentiate into?
B-2
Two subsets of B-2 include:
Follicular B cells
Marginal B cells
Follicular B cells
of the B-2 subset
re-circulating B cells (Majority)
give rise to long-lived plasma cells (IgG, IgE, IgA)
see protein antigens and require helper T cells
spleen and other lymphoid organs
Marginal B cells
of the B-2 subset
reside in the spleen DON”T recirculate
respond to blood-borne polysaccharide antigens
make predominantly IgM
Membrane bound Ig does not have…
cytoplasmic tail… so it cannot signal
all of signalling from binding of mIg comes from the Ig-alpha and Ig-beta and B cell co-receptors.
Antigen dependent phase
Response initiated by recognition of antigen (its epitope) by B cell specific for that antigen (idiotope)
Antigens binds to membrane Ig on naive cells and activates these cells
activation can be T dependent or T independent
T cell dependent
some T cells stimulate, or help, B lymphocytes to produce antibodies
In the absence of T cell help, protein antigens elicit weak or no antibody responses
Protein antigens are processed in antigen-presenting cells (APCs) and recognized by helper T lymphocytes, which play an important role in B cell activation and induce heavy-chain isotype switching and affinity maturation.
T independent
Polysaccharides, lipids, and other nonprotein antigens stimulate antibody production without the involvement of helper T cells
The antibodies produced in response to T-independent antigens show relatively little heavy-chain isotype switching and affinity maturation.
Naive B cells in circulation
Travel through secondary lymphoid tissue
enter from blood if going to spleen
in lymph if going into nodes
migrate to primary lymphoid follicles which contain FDC’s
enter through HEV
if they don’t encounter antigen they migrate to primary follicle
receive signal to survive from FDC’s
exit through efferent lymphatic vessels
competition of B cells for survival signals
too many B cells, not enough FDC’s to provide signals for survival
naive b cells die within weeks in absence of antigen
L selectin
expressed on naive b cells
binds to peripheral node addresin (PNAd)
what does CCR7 bind and where is it expressed
expressed on Naive B cells
binds to CXCL19 or CXCL21 on lymph node HEV’s
What do naive b cells express
L selectin
CCR7
LFA1
CXCR4
what does LFA1 bind?
ICAM-1 on lymph node HEV’s
what does CXCR4 bind to ?
CXC12 on lymph node HEV’s
B cell homing
Cytokines produced by HEV and stromal cells activates integrins
B cell migrates to follicular zone by CXCL13
Dendritic cells migrate in from periphery and bring in antigen (attracted to CCL21)
Dendritc cells secrete CCL18 and CCL19 which attract T cells to the lymph node
B cells respond to CXCL19 and once in the lymph node they migrate to where the FDC’s are secreting CXCL13
CXCL13
Mediates follicle migration
is secreted by Follicular dendritic cells (FDC’s) in the lymph node which attracts more B cells
B cell activation first signal (one type)
Ag recognition by membrane bound Ig’s
Must crosslink 2 or more BCR
Signaling occurs through Igalpha and Igbeta cytoplasmic tails
prepares cell for interaction with 2nd signal
at this point it is minimally activated