Lecture 14: B Cell activation and Antibody Production Flashcards
Primary response differs from secondary response how
Secondary is - More rapid Larger amounts of Abs produced Isotype switching of heavy chain occurs Affinity maturation occurs
Antibody responses to what do not require Ag-specific helper T lymphocytes
Multivalent non-protein Ags with repeating epitopes, such as polysaccharides, some lipids, and nucleic acids
Antibody responses to what require CD4+ T cell help
Protein antigens
What facilitates the formation of germinal centers, and what happens in these centers
Follicular helper B cells
Activated B cells proliferate here
Follicular B-2 cells respond to
Protein Ags and thus initiate T-dependent Ab responses
Marginal zone B cells respond to
Multivalent Ags and are T independent
B-1 cells in mucosal sites respond to
Multivalent Ags and are T independent
B-1 B cells arise from where
Fetal liver
What guides the movement of Follicular B cells into the follicles of secondary lymph organs
CXCL13 chemokine secrected by resident follicular DCs
It attracts Naïve B cells to follicules
Soluble Ag fate in delivery to LN
Small Ags (Smaller than 70kD generally) may reach B cell zone of the follicle and interact directly with specific B cells
Large Ag fate in delivery to LN
May be captured by resident FDCs and transported into follicles where they can activate B cells
Microbe/Ag-Ab complex fate in delivery to LN
Captured by subcapsular sinus macrophages which deliver Ags to follicles
FDCs have unique capacity to retain
Immune Ag-Ab complexes on their surface for long periods (weeks to months)
Ag retention by FDCs is mediated by
FcyRIIB Fc receptors or CR1/CR2 (CD21) complement receptors
Follicular B cell survival depends on
Signals from BCR as well as inputs received from cytokine BAFF (B cell activating factor of the TNF family)
BAFF is produced by
Myeloid cells in lymphoid follicles and bone marrow
T or F: FDCs express class II MHC
False
And they do not phagocytose/process exogenous Ags for Class II MHC
B-T cell interaction leads to
Minimal isotype switching, and generation of short lived plasma cells mainly producing IgM
- B cells then migrate to germinal centers and undergo :
- somatic mutation
- affinity maturation
- isotype switching
- generation of memory B cell and long lived plasma cells
Generation of Tfh cells requires
Sequential activation of T cells, first by DCs and then by B cells. The Tfh cells then migrate to GCs where they activate B cells
Tfh cells are drawn into lymphoid follicles by
CSCL13, they play a critical role in GC formation and function
Tfh cells express
ICOS, PD-1, IL-21 and Bcl-6
IL-21 importance in GC
Important in GC for development of B cells, isotype switching, affinity maturation and antibody production
What happens in the dark zone of GC
Activated B cells migrate into area and proliferate.
They undergo extensive isotype switching and somatic hypermutation of Ig V genes here
What happens in the light zone
B cells encounter follicular DCs displaying Ag and Tfh cells
Ab secreting cells go where, memory B cells go where
Ab secreting cells reside in bone marrow as long lived plasma cells
Memory B cells enter the recirculating lymphocyte pool
Mantle zone
Surrounds GC and contains tightly packed small B cells of the primary follicles, pushed aside by GCs
The expression of what induces migration of B cells toward the T cell zone
CCR7
T or F: Marginal zone B cells mount rapid Ab responses to both T cell dependent and T c ell independent antigens
True
MZ B cells respond to
Blood borne viruses and encapsulated bacteria by using ‘crossover’ defensive strategies
MZ B cell activation threshold compared to follicular B cells– this permits what
MZ B cells have lower activation threshold, which permits rapid initiation of IgM production and of IgG/IgA class switch recombination in the absence of CD40 dependent help from Tfh cells
This T cell independent pathway that MZ B cells use requires
Dual BCR and TLR engagement by conserved microbial Ags together with co-stimulatory signals from DCs and macrophages via various cytokines
The Ags presented to MZ B cells are generally in
Native conformation, not processed by APCs
Ags in immune complexes may bind what on MZ B cell, who then do what
Bind CR@ complement receptor
MZ B cells can then transfer the immune complexe-containing Ags to follicular DCs
Blood borne pathogens are captured by what for transfer to the spleen
Plasmacytoid DCs
Polysaccharide Ags in spleen captured by who
MZ macrophages and are then displayed or transferred to MZ B cells in area
Ag presenting MZ macrophages stimulate MZ B cells via
BCR and TLRs
Stimulation of MZ B cells by MZ macrophages delivers signal that causes
CSR and Ab production, after ligating BAFF and APRIL (a proliferation inducing ligand) - which are released by APCs in response to microbial TLR ligands
