Chapter 12 B-Cell Activation and Differentiation Dr. Capers Immunology

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) – lipopolysaccharide Type 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

Membrane Ig must be associated with B-cell receptor 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 receptor Ig-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 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 centers Affinity maturation Result of somatic hypermutation Class switching Formation of plasma and memory B cells

Cellular events in germinal centers Dendritic cell presents antigen to developing B cells to see which B cells are producing antibody with high-affinity for 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 antigen Some vaccines are given to babies after maternal IgG (that was transferred across placenta) has left system Vaccination before this will prevent proper response and development of long-lasting memory cells