PHSC1312 Microbiology/Immunology Lecture 15 B Lymphocyte Development & Priming

Pre B cell

undergoes V-D-J recombination to rearrange the genes resulting in the heavy (H) and light (L) chains of the B cell receptor

Heavy and light chains of B cell receptor

result of a pre-B cell undergoing VDJ recombination

Rag1 and Rag2

enzymes that orchestrate the rearrangement of the V, D, J segments on the heavy and light genes

Rearrangement on kappa or lambda chain

What choice do light chains have during VDJ recombination?

After recombinaton on light and heavy chains

When is a B cell committed to making an antibody with only one antigen specificity?

Heavy

Which BCR chain undergoes rearrangement first?

2 heavy, 2 light

How many light and heavy chains make up a BCR/antibody?

Disulfide bonds

What type of bonds link the heavy and light chains of a BCR/antibody?

Antigen binding site

made by variable heavy and light chains

Variable heavy and light chains

make up the antigen binding site

Carboxy terminal

What end has the BCR membrane bound until B cell activation by its cognate antigen?

Activation by cognate antigen

What has to happen for the BCR to not be membrane bound at the carboxy terminal end?

2

How many antigen binding sites does every antibody molecule have? (if no oligomerization)

Constant

What region determines the different antibody isotypes?

Mu, delta, gamma, epsilon, alpha

five constant regions that give the different isotypes

IgM

first antibody made

Mu

constant region initially closest to the variable region?

Bone marrow

Where does B cell selection occur?

Positive and negative selection

2 parts to B cell selection

Positive

selection where only B cells expressing functional BCR receive "positive" signals to survive

Bruton's tyrosine kinase

molecule that signals to the cell to continue to divide and differentiate

BTK inhibitors

therapeutic options for stopping B cell division and differentiation

Functional

Positive selection indicates if a B cell receptor is what?

Positive signals to survive

What do only B cells expressing functional BCR receive in positive selection?

Negative

selection where any autoreactive immature B may have to undergo receptor editing and if it fails, then they die

Autoreactive

feature of immature B cells in negative selection that would induce receptor editing

Receptor editing

process that induces autoreactive immature B cells to change specificities

Apoptosis or anergy

What happens to the immature B cells if receptor editing fails?

Anergy

protective strategy where B cells become unresponsive to antigen

Mature naive B cells

exit the bone marrow with a unique BCR

Antigen specificity

When activated, all clones will have the same what as the original cell?

Whole 3D structural epitopes

What can BCRs detect?

Sugars, lipids, nucleic acids, proteins

examples of whole, 3D structural epitopes

B cell zone

Where do B cells reside in secondary lymph tissues?

CXCR5

chemokine that calls B cells to B cell zone; must be upregulated by T cells for entry

CXCR5 upregulation

How do T cells enter the B cell zone?

Affinity for antigen

What gets increased during class switching?

Plasma cell

factory for antibodies of the B cell that it originates from

Spleen

B cell rich secondary lymph tissue

T cell independent and T cell dependent

2 types of B cell activation

Antigens T cells can't recognize

What is T cell independent B cell activation good for?

Strong activation, clonal expansion, and differentiation

What happens after the multivalent antigen crosslinks multiple receptors, C3b opsonizes, and a PAMP interacts?

CD4+

What T cells are involved in T cell dependent B cell activation?

Less receptor ligation

What is different about receptor antigen interaction in T cell dependent B cell activation?

Protein

What does the antigen have to contain to go undergo T cell dependent B cell activation?

Weak activation or sensitization

What happens to the B cell when the protein binds to the receptor, but it isn't a very strong signal?

Antigen presentation

After being weakly activated or sensitized, what does the B cell begin?

BCR mediated endocytosis

process where the B cell takes in the whole antigen receptor complex

T cell zone

Where are the T helper cells primed?

MHC II

What did the dendrite present the antigen source on for the CD4+ T helper cells?

Same antigen

What do the sensitized B cell and primed T cell recognize?

Strong activation, clonal expansion, and differentiation

What happens after the following events happen: B cell presents cognate peptide T cell has been primed against, and T cell delivers costimulation through CD40L and IL21?

Class switching and somatic hypermutation

What do we get in T cell dependent B cell activation that drives a more effective and efficient antibody response long term?

Antigen recognition and inflammation

two activation signals of B cells

Multivalent antigens cross link many BCRs

signal 1 (antigen recognition) for T cell independent B cell activation

Antigen with protein source

signal 1 (antigen recognition) for T cell dependent B cell activation

Signal 2

Which signal in B cell activation is a safety step to avoid unwanted B cell activation?

Stimulation by PAMPs or through C3b detection by B cell

signal 2 (inflammation) for T cell independent B cell activation

Costimulation and cytokines by helper T cells

signal 2 (inflammation) for T cell dependent B cell activation

CD40 and CD40L

costimulation signal for signal 2 in T cell dependent B cell activation

IL21

cytokine produced by Th cells in the germinal center for signal 2

T cell independent

B cell activation that is shorter lived and has limited class switching; IgM produced and maybe some IgG

Multivalent

What type of antigens crosslink B cell receptors in T cell independent B cell activation?

T cell dependent

B cell activation with long-lived antibody production (huge memory pool); specific antibody responses; IgE, IgG, IgA

Load peptides from antigen on MHC II for presentation to CD4+ T cells

What do sensitized B cells do?