Antigen Recognition and T-Dependent Humoral Response of B Lymphocytes- Exam 4

Micro 4110 Exam 4

T-independent humoral response

B cells work alone- mediocre antibodies produced

T-Dependent Humoral response

B cells working with T cells- much stronger antibodies produced

B cell ineraction with antigen

Binary complex of membrane Ig and BCR

T cell interaction with antigen

Ternary complex of TCR, Ag, and MHC molecule

Binding of soluble antigen

Yes for b cells, no for t cells

Involvement of MHC molecules

None required for B cells, required for t cells

What antigens do b cells recognize

Protein, polysaccharide, lipids

What antigens do t cells recognize

Proteins

Epitopes recognized by b cells

Surface level, conformational, can be sequential or nonsequential

Epitopes recognized by t cells

Internal, linear, only sequential

B cell activation

Requires 2 signals, both are essential

1st signal of B cell activation

Antigen binding to BCR causes clustering or cross-linking of 2 or more BCRs (membrane Ig receptors)- activates B cell signaling pathways

2nd signal of B cell activation

CD40 and CD40L interaction, provided by helper T cells, activates a cytokine release

CD40

Always present on B lymphos

CD40L

Only present on effector helper T cells

How do helper T cells help activate B cells

By presenting the second signal via CD40 ligand

How do helper t cells find b cells to activate them

When a b cell binds to an antigen, it endocytoses and digests it, then displays the peptides in its MHC II complexes on its surface, This allows TFH cells to recognize and deliver the CD40L signal to the CD40 on the B cell

Linked recognition

T and B cells working together to recognize the same antigen, but at different epitopes- these epitopes are physically connected on the same antigen

1st phase of T-dependent humoral response

Plasma cells and IgM antibody secretion

2nd phase of t-dependent humoral response

Somatic hypermutation, affinity maturation, isotype switching, and memory b cells

Proliferation of B cell

B cell that is activated by antigen and has received co-stimulatory signals and cytokines from TFH begins to multiply and expand its clone

B cell differentiation

While proliferating, b cells differentiate in two phases. The first takes place in the medullary cords, and the second takes place in the germinal center within the follicular area

Phase 1 of b cell differentiation

Multiplying b cells move into the medullary region of the lymph node and differentiate into plasma cells, secreting IgM antibodies

Phase 2 of b cell differentiation

Within the follicular region of the lymph node the activated b cell proliferates and establishes a germinal center, where somatic hypermutation and affinity maturation take place. Creates much better antibodies than phase 1

Germinal center

The area of a follicular region where there is a range of cell types- center is made of rapidly dividing b lymphos and plasma, but memorby b cells, TFH and follicular dendritic cells are also present.

Somatic hypermutation

AID introduces rapid mutations in the V-region of L and H chains of the BCR, changing how well the antigen binds to the BCR. This ultimately has an effect on the quality of antibodies produced

V-region

Variable region, composed of both heavy and light chains, and is responsible for antigen binding to the BCR

AID

Activation-induced cytidine deaminase- the enzyme that introduces the mutations in somatic hypermutation

Affinity Maturation

B cells with mutations that improve affinity for antigen are preferentially selected for survival because of their greater ability to bind to the antigen. The BCR with the highest binding affinity will outcompete the others for access to the limited antigen, endocytose the antigen, and display the peptides on its surface. The t cell can then bind to the peptides, which is the survival signal. All other B lymphos that don’t get this survival signal die

Survival signal

Come from TFH and CD40 signaling- same as the signals required for b cell activation

What happens to positively selected b cells

They differentiate into antibody secreting plasma cells