Chapter 12B-Cell Activation and Differentiation
Dr. Capers
B cell activation B cell encounters specific antigen B cell presents to T helper cell Cytokines are released for full B cell activation Proliferation, some of the B cells become
plasma cells Some of the B cell clones move to germinal
centers of lymph nodes, somatic hypermutation can occur
Class switching occurs
The tiny region of the antigen that BCR actually binds to is called its “epitope”.
The epitope will be the part of that protein (usually 6 – 12 amino acids) to which the BCR receptor binds.
When the BCR recognizes the epitope, for which it is matched, it must signal this recognition to the nucleus of the B cell, where genes involved in activating the B cell can be turned on or off.
B cell Activation Thymus-dependent (TD) antigens
B cell required direct contact with TH cell B-2 B cells, majority of B cells
Thymus-independent antigens (TI) These antigens activate B cells by pattern recognition
receptors (bacteria that might be in high amount)Type I (TI-1) – lipopolysaccharideType 2 (TI-2) – highly repititous molecules (bacterial
flagella)
B cell Activation Membrane bound
antibody have short cytoplasmic tails
○ Too short to generate signal by associating with tyrosine kinases and G proteins
So that the external part of the BCR can signal what it has seen, B cell are equipped with two accessory proteins
Membrane Ig must be associated with B-cell receptorIg-α/Ig-β
ITAMS ITAMs are important for signal
transduction in immune cells. An ITAM is a specific sequence of amino acids occurring twice in close succession in the intracellular tail of a receptor
They are found in the tails of important cell signaling molecules such as the CD3 and ζ-chains of the T cell receptor complex, the CD79-alpha and -beta chains of the B cell receptor complex, and certain Fc receptors.
The tyrosine residues within these motifs become phosphorylated following interaction of the receptor molecules with their ligands and form docking sites for other proteins involved in the signaling pathways of the cell
ITIM (immunoreceptor tyrosine inhibitory motif)
○ Associated with CD22
○ Functions to deactivate B cells – negative regulation
○ Important in preventing autoimmunity
TH cells play essential role in B cell repsonses
Remember: B cells can be t-cell independent or dependent!
TEM of interaction between B cell and T cell
Humoral Response – Primary vs Secondary
Hapten-carrier conjugates Hapten – low molecular weight molecule
that can elicit an immune response only when attached to a large carrier such as a protein.
In vivo sites for induction of humoral responses Bloodborne antigen is filtered by spleen Antigen from tissue spaces filtered by lymph
nodes○ Antigen either enters alone or with antigen-
transporting cells- Langerhans cells (antigen-presenting immune cells) of the
skin and mucosa- Dendritic cells
○ Encounters antigen-presenting cells- Dendritic cells- Macrophages- Follicular dendritic in follicles and germinal centers
T cells are green and B cells are red
Germinal centers arise within 7-10 days after initial exposure to thymus-dependent antigen in lymph node
○ 3 events in germinal centersAffinity maturation
- Result of somatic hypermutationClass switchingFormation of plasma and memory B cells
Cellular events in germinal centers
Dendritic cell presents antigento developing B cells to seewhich B cells are producingantibody with high-affinityfor that antigen
Class Switching Dependent on cytokines to
switch from IgM to other isotype Thymus-dependent
antigens Interaction of CD40 on B
cell and CD40L on T cell X-linked hyper-M syndrome
○ TH cells don’t express CD40L, patients only produce IgM No memory cell populations,
no germinal centers
Regulation Humoral and cell-mediated branches must be heavily
regulated Cytokines play important role Antigenic competition
Previous encounter with antigen can render animal tolerant or may result in formation of memory cells
Presence of antibody can suppress response to antigenSome vaccines are given to babies after maternal IgG
(that was transferred across placenta) has left systemVaccination before this will prevent proper response
and development of long-lasting memory cells
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