[M4] Topic 3: B Lymphocyte Activation and Differentiation

What do B cells give rise to during an immune response?

Plasma cells

What do plasma cells secrete?

Antibodies

What is the role of antibodies in immunity?

Destroy extracellular pathogens and their products, and prevent the spread of intracellular pathogens

Where do B cells develop and generate unique receptors?

In the bone marrow

What processes do B cells undergo in the bone marrow to ensure non-self-reactivity?

Positive and negative selection

What do immature B cells express before maturation?

IgM receptors

What do mature B cells express after full development?

Both IgM and IgD receptors

Where do mature, naïve B cells recirculate?

Among the blood, lymph, and secondary lymphoid organs

What type of Ig receptors does each circulating B cell bear?

Receptors of a single specificity

What happens when a B cell binds to its specific antigen?

It undergoes clonal selection

What is produced during clonal selection?

A clone of cells bearing the same antigen receptor as the original B cell

Where do mature B cells migrate after maturation?

To lymphoid follicles

What happens if a B cell does not encounter antigen?

It recirculates through the blood and eventually dies by apoptosis

What is the first signal needed for B cell activation?

BCR engagement

What is the second signal type needed for B cell activation?

T-dependent (TD) or T-independent (TI) antigen signaling

What do activated B cells differentiate into?

Effector cells (plasma cells) and memory B cells

What is the role of plasma cells?

To secrete antibodies

Where do B cells typically encounter antigen?

In the lymph nodes or spleen

What happens when a BCR binds a soluble antigen?

Clustering of antigen-bound BCR molecules occurs in the plane of the membrane

What kinase initiates the signaling cascade by phosphorylating ITAMs on Igα/β?

Lyn

What do phosphorylated ITAMs serve as?

Docking sites for other signaling proteins

What is the final result of the BCR signaling cascade?

Activation of transcription factors and their translocation into the nucleus

What does antigen receptor clustering induce in B cells?

Internalization of the antigen and presentation

What happens to BCR-antigen complexes once signaling begins?

They are endocytosed

What pathway is used to process internalized antigen in B cells?

The exogenous pathway

What happens to the antigen after it is internalized by the B cell?

It is broken down into peptide fragments

What molecules present the antigenic peptides on the B cell surface?

MHC class II molecules

What costimulatory molecules are upregulated on B cells after antigen engagement?

CD40 and CD80/CD86

What type of antigen typically triggers a T-dependent (TD) response?

Protein antigens

What type of T cell is required for T-dependent B cell activation?

CD4+ helper T cells

What is Signal 1 in a T-dependent B cell response?

B cell binds antigen via its Ig receptors

What happens to some of the bound antigen in a TD response?

It is processed and presented to helper T cells via MHC class II

What is Signal 2 in a TD response?

CD40 on the B cell interacts with CD40L on the T cell

What is Signal 3 in a TD response?

The T cell delivers activating cytokines to the B cell

What type of antigens trigger a T-independent (TI) response?

Polyvalent, repeating determinants shared among many microbial species

Does T-independent B cell activation require T cell help?

No

What provides Signal 1 in a TI response?

Antigen binding to membrane-bound Ig (mIg) on B cells

What provides Signal 2 in a TI response?

Simultaneous engagement of innate immune receptors or complement receptors (e.g., CD19/CD21)

How can antigens enhance B cell activation in a TI response?

By being opsonized with complement components and cross-linking mIg with CD19/CD21

What is the structural composition of the B-cell receptor (BCR)?

It is a quaternary protein with two identical heavy chains and two identical light chains.

What is the Fab region of the BCR responsible for?

Antigen binding

How is antigen specificity determined in the Fab region?

By interactions between the variable regions of the light and heavy chains

What is the Fc region of the BCR responsible for?

Effector functions such as phagocytosis and complement fixation

What determines the effector activity of the antibody?

The constant region of the heavy chain

What determines the antibody isotype in a B-cell receptor?

The constant region of the heavy chain

What is the heavy chain associated with IgA?

Alpha (α)

What is the heavy chain associated with IgD?

Delta (δ)

What is the heavy chain associated with IgE?

Epsilon (ε)

What is the heavy chain associated with IgG?

Gamma (γ)

What is the heavy chain associated with IgM?

Mu (μ)

Where does CSR occur after antigen contact?

In the lymph node or spleen

What costimulatory signal is required for B cells to undergo CSR?

CD40 engagement (Signal 2)

What determines the antibody isotype produced during CSR?

The cytokine signal received (Signal 3)

What isotype(s) are produced in response to IL-4?

IgG1, IgE

What isotype(s) are produced in response to TGF-β?

IgA, IgG2b

What isotype is produced in response to IL-5?

IgA

What isotype(s) are produced in response to IFN-γ?

IgG3, IgG2a

What enzyme initiates class switch recombination?

AID (activation-induced deaminase)

What triggers CSR in activated B cells?

Antigen contact and costimulatory signals, including cytokines and CD40 engagement