Lecture 27 (B cell module) Flashcards
What signals does activation of B cells require
1) Signal 1–> p:BCR
2) Signal 2–> TCR:pMHCII (peptide presented by B cell) (CD40L:CD40)
3) Additional costimulatory signals and cytokines
4) Linked recognition
What is Humoral Immunity
When antibodies promote pathogen neutralization, opsonization, and complement activation
What induces activated B cells to produce specific types of antibodies?
Secreting IL-21 and either Type 1 (INFgamma), Type 2 (IL-4), or Type 3 (IL-17) cytokines
What cells directly interact with B cells
TFH cells
What antibody class serves as a receptor on Naive B cells
IgM
Where do B cells arise
Bone marrow
Main characteristics of B cells (innate immunity)
1) Antigen specific
2) Clonotypic
3) Progenitors of antibody producing plasma cells and plasmablasts
BCR is?
Membrane bound
Action once B cell is activated
Secretes BCR (antibody)
Overall process of clonal selection
Activated B cells undergo proliferation and differentiation–>plasma cell that secretes antibodies (outcome)
Where do B cells circulate?
In periphery and through lymph nodes and spleen
Entry and exit of B cells through the lymph node
Entry–>High Endothelial Venules (HEV)
Exit–>Efferent Lymphatics
Outcome of B cell encountering or NOT encountering Antigen
B cell + no antigen–>dies of apoptosis after a few months
B cell + antigen–>provides survival signal (signal 1)
How do antigen end up in lymph node
1) Antigens from pathogens via afferent lymphatics
2) Antigens opsonized by complement pathway
3) Antigens transported by activated conventional Dendritic cells (antigen then transferred to follicular DC in lymph node)
What retains antigen in lymph node
Subscapular sinus macrophage (SCS macrophage)
Mechanism of how antigen is retained in lymph node
Subscapular sinus macrophage (SCS macrophage) express complement receptor on surface–> complement receptor binds to complement on opsonized antigen–>antigen retained in lymph node
SCS macrophage trait
Low endocytic and low degradative activity
What co receptor does B cell express
Complement receptors CD19 and CD21 (binds complement to enhance signaling and activation)
Main outcomes of BCR:AG signaling
1) Transcription factors are activated leading to gene transcription
2) Survival signal (signal 1)
3) Cytoskeletal reorganization
Pathway used to process antigen and the MHC class in B cells
Exogenous pathway and MHC class II
What provides Signal 2
Activated CD4+ TFH Cell and TLR signaling
Specific binding that induces Signal 2
1) pMHC binding to TCR and co-receptor on TFH cell
2) CD40 on B cells binding to CD40L on TFH cells
Difference between recognition of Antigen by B cells vs T cells
B cells: recognize antigen in natural form
T cells: recognize antigen presented on MHC on the surface of APCs