B cell activation and antibody production (part I) Flashcards
mature Ag-responsive B cells develop from bone marrow precursors in the absence of ____
Ag
Ag activate mature naive B cells by binding to membrane ____ and/or ____
IgM and/or IgD
at the peak of humoral immune response, about ____ Abs are produced every day
1012
in primary immune response, naive B cells are stimulated by Ag, become activated, and differentiate into Ab-secreting cells that produc more ____ than ____ specific for the eliciting Ag
IgM than IgG
secondary immunte resposes are elicited when the same Ag stimulates memory B cells, leading to production of more ____ than ____
IgG than IgM
primary response can be thought of as T Cell-____
independent
secondary response can be thought of as T Cell-____
dependent
T Cell-dependent:
- occurs ____ follicle/GC
- must be ____ Ag
- affinity ____
- isotype ____
- ____-lived plamsa cells
- what B cells assist:
- in
- protein
- maturation
- switching
- long-lived
- follicular B cells
T Cell-independent:
- occurs ____ follicle/GC
- ____ Ag
- no affinity ____
- no isotype ____
- ____-lived plasma cells
- what B cells:
- outside
- non-protein (multivalent)
- maturation
- switching
- short-lived
- MZ B Cells, and B1 Cells
follicular B-2 cells respond to ____ Ags and thus initiate T Cell-____ Ab responses
protein Ags
T Cell-dependent
marginal zone B cells respond to ____ Ags and are T Cell-____
multivalent Ags
independent
B-1 Cell in ____ sites respond to ____ Ags and are T Cell-____
mucosal sites
multivalent Ags
T Cell-independent
most mature naive B lymphocytes are ____ cells which are also called recirculating B cells or ____ cell
follicular cells
B-2 cells
in secondary lymphoid organs, folliclar B cells migrate into the B cell zones of these tissues called
follicles
the ____ chemokine secreted by resident follicular DCs guides the movement of B cells within secondary lymphoid organs
CXCL13
what types of Ags are delivered to follicular B cells by direct delivery
small, soluble Ags (bind to B cells in the follicle)
what types of Ags are delivered to follicular B cells by indirect delivery?
Large Ags and immune complexes (Ag-Ab) are captured by sinus macrophages or by resident follicular DCs
properties of follicular DCs:
- are not ____
- do not express ____ molecules
- do not ____ Ags
- do not ____ Ag in Class I MHC
- Ag retention (for long periods) is mediated by ____ , ____ , or ____
- professional APCs
- MHC II
- phagocytose
- cross-present
- FcgammaRIIb , CR1 , CR 2
follicular B cell activation:
- BCR signaling starts activation and triggers ____ of Ag
- Ag is processed and presented to T helper cells via ____ after B and T lymphocytes migrate towards one another
- T helper cells provides additional signals for activation and differentiation into short-lived plasma cells (produce IgM) ( ____ and cytokines )
- follicular B cell migrates back into GC where ____ from myeloid cells acts as survival signal and B cell can undergo somatic mutation, affinity maturation, isotype switching, geneneration of memory B cells and long-lived plasma cells (produing all isotypes)
- endocytosis
- MHC II
- CD40
- BAFF
____ and ____ may enhance B cell activation
CR2 and TLRs
extrafollicular B cell activation:
- BCR signaling starts activation and triggers ____ of Ag
- Ag is process and presented to T helper cells via ____ after B and T cells migrate towards one another (outside of GC)
- T helper cell provides additional signals for activation and differentiation into plasma cells ( ____ and cytokines)
- plasma cells produced are ____-lived and produce ____
- endocytosis
- MHC II
- CD40
- short-lived IgM
Tfh express ____ (receptor for CXCL13) → migration to ____
CXCR5
GC
Tfh express IL-21 → stimulates ____ ____ , affinity ____ , and transition to ____
isotype switching , affinity maturation , and transition to plasma cells
activation/differentiation of Tfh cells:
- naive T cell presented ____ by DC
- T cell expresses ____ and ____
- stimulus for differentiation via ____/____ interaction with B cell
- migration into ____
- Ag
- CXCR5 and Bcl-6
- ICOS/ICOS-L
- GC
FDCs secrete ____ to attract B and Tfh cells → creation of ____ ____
CXCL13
germinal centers
germinal center organization and stimulation by ____ of FDCs and functionally requires ____ from Tfh cells
CXCL13
IL-21
3 zones in germinal center
dark
light
mantle
3 zones in germinal center:
Dark Zone
- where ____ cells enter the GC and proliferate
- these cells undergo extensive ____ ____ and somatic ____ of Ig variable genes
Light Zone
- B cells migrate into the light zone where they encounter ____ displaying Ags and Tfh cells
- B cells undergo ____
Mantle Zone
- pushed aside B cells from primary follicle that are ____ the CG
Dark Zone
- B cells
- isotype switching hypermutation
Light Zone
- FDCs
- selection
Mantle Zone
- outside
3 zones of spleen
red
white
marginal zone
Spleen- white pulp characteristics:
1.
2.
3.
- PALS (around arteriole) - T cell zone
- follcile (B cell zone) - similar process to LNs
- contains plasma cells
spleen- marginal zone characteristics:
1.
2.
- between red and white pulp
- location of MZ B cells
lymphocyte and DCs can enter the white pulp from the ____ ____
marginal sinus
MZ B cells mount raid Ab response to both ____ and ____ Ags
T-dependent and T-independent
MZ B cells have relatively ____ threshold compared to other B cells allowing for rapid resposne early in infection
low
MZ B cells produce rapid initiation of ____ production and can also produce ____ and ____ without help from Tfh cells
IgM
IgG and IgA
MZ B Cells:
T Cell-indepednent pathway requires dual ____ and ____ engagement by conserved microbial Ags together with co-stimulatory signals from DCs and macrophages
BCR and TLR
