HI12 - B Cells Part I

Biomedical Sciences I

What is the overall process by which B Cell receptors and antibodies gain diversity?

Somatic recombination, which rearranges gene segments to produce unique B Cell receptors and antibodies.

What are the two types of light chains found in antibodies?

Kappa (κ) and Lambda (λ) light chains.

What are the five isotypes of heavy chains in antibodies?

IgA, IgG, IgD, IgE, and IgM.

Which antibody component determines its function?

The heavy chain.

Which antibody component determines its antigen specificity?

The combination of heavy and light chains.

What are the two fragments formed when antibodies are enzymatically cleaved?

Fab (antigen-binding) and Fc (constant region).

What does the Fab region determine?

Antigen specificity.

What does the Fc region determine?

Antibody function (interacts with immune cells and complement).

What is the purpose of the hinge region in antibodies?

It provides flexibility, allowing both Fab arms to bind antigens spaced at varying distances.

What are hypervariable regions?

Short, variable loops in heavy and light chains that form the antigen-binding site.

What types of molecules can antibodies recognize?

Proteins, glycoproteins, carbohydrates, glycolipids, peptidoglycans, nucleic acids, and small molecules.

Which type of antigen is most immunogenic for antibody responses?

Proteins, because they can be recognized by CD4+ T Cells and induce strong immune responses.

Why can’t CD4+ T Cells help activate B Cells that recognize non-protein antigens?

CD4+ T Cells only recognize peptide antigens presented by MHC Class II molecules.

Define affinity in antigen-antibody interactions.

The strength of a single antibody-antigen binding interaction.

Define avidity in antigen-antibody interactions.

The combined strength of all interactions between an antibody and an antigen.

Which heavy chain variant has high affinity but low avidity?

IgG, which has 2 high-affinity binding sites.

Which heavy chain variant has low affinity but high avidity?

IgM, which has 10 low-affinity binding sites.

What are the three gene loci involved in antibody recombination?

Two light chain loci (kappa and lambda) and one heavy chain locus.

What enzyme mediates somatic recombination in B Cells?

RAG (Recombination Activating Gene).

What sequences does RAG recognize during recombination?

Recombination Signal Sequences (RSS).

What are P-nucleotides and N-nucleotides?

They are added during recombination to increase junctional diversity.

What are the two sources of antibody diversity?

Combinational diversity (V(D)J selection) and junctional diversity (P- and N-nucleotide addition).

What is the theoretical number of possible antibody molecules due to recombination?

Approximately 5 × 10¹³ (50 trillion).

Where do B Cells develop in mammals?

In the bone marrow.

What is the correct sequence of B Cell development stages?

Lymphoid progenitor → Early Pro-B → Late Pro-B → Pre-B → Immature B → Mature Naïve B → Activated B → Effector Cell.

What type of change is somatic recombination (DNA-based or RNA-based)?

DNA-based and irreversible.

What type of change is isotype co-expression (IgM and IgD)?

RNA-based and reversible.

What happens in the Pro-B Cell phase?

Heavy chain recombination occurs: D–J rearrangement first, then V–DJ.

What is Checkpoint 1 during B Cell development?

Tests whether the rearranged heavy chain can pair with a surrogate light chain to form a Pre-B Cell receptor.

What happens if the first heavy-chain rearrangement fails at Checkpoint 1?

The cell tries rearranging the other allele before apoptosis.

What signal does a successful pre-B-cell receptor give?

Survival, proliferation, and allelic exclusion for the heavy chain.

When does a B cell undergo apoptosis after Checkpoint 1?

Only if all heavy-chain rearrangements fail to produce a functional pre-BCR.

What happens after a B cell passes Checkpoint 1?

The cell proliferates, stops heavy-chain rearrangement (allelic exclusion), and begins light-chain recombination.

What happens during the Pre-B Cell phase?

The light chain genes (κ and λ) undergo somatic recombination.

What is Checkpoint 2 during B Cell development?

Tests whether the heavy and light chains form a functional receptor (IgM).

What happens if a B Cell fails Checkpoint 2?

It cannot form a functional B cell receptor (IgM) and undergoes apoptosis.

What is central tolerance?

The process of removing autoreactive B cells in the bone marrow.

What are the three outcomes for autoreactive B cells in the bone marrow?

Receptor editing, apoptosis, or anergy (non-responsiveness).

What is receptor editing?

The reactivation of RAG to rearrange new light-chain genes and eliminate self-reactivity.

When does receptor editing stop?

When the B cell produces a non-self-reactive receptor or when all light-chain segments are exhausted, leading to apoptosis.

What happens to immature B cells that react with multivalent self-antigens?

They are retained in bone marrow and undergo receptor editing.

What happens to immature B cells that do not react with self-antigens?

They leave bone marrow, begin expressing IgD, and enter circulation.

What is anergy in B cells?

A state where B cells that bind soluble self-antigen become non-responsive and downregulate surface IgM.

What receptor is downregulated during anergy?

IgM.

What receptors do immature B cells express?

High IgM, low IgD.

Where do immature B cells finish maturation?

In secondary lymphoid follicles.

What cells support B cell maturation in follicles?

Follicular dendritic cells (FDCs).

Do follicular dendritic cells present antigen via MHC II?

No. FDCs are non-phagocytic and present unprocessed antigens using complement receptors, not MHC molecules.

What factor promotes B-cell maturation in follicles?

BAFF (B Cell Activating Factor) from follicular dendritic cells.

What percentage of immature B cells successfully mature?

About 20%.

What is the half-life of mature, naïve B cells without antigen?

Around 100 days

What triggers isotype switching in activated B cells?

CD4⁺ T-cell help and cytokine signaling.

Is isotype switching reversible?

No, it is a DNA-based, irreversible process.

What is the first heavy-chain isotype produced by B cells?

IgM is always produced first.

What are the two main mature B cell types?

B-1 and B-2 B cells.

Where do B-1 B cells develop?

In the fetal liver and omentum.

What are B-1 B cells specialized for?

Low-affinity, broad binding to carbohydrate antigens.

Do B-1 B cells undergo somatic hypermutation or class switching?

Little to none — they act like innate-like B cells.

What percentage of adult B cells are B-2 cells?

About 95%.

What does humoral immunity rely on?

Soluble antibodies in blood, lymph, and secretions.

What does cellular immunity rely on?

Immune cells like macrophages, CD4⁺, and CD8⁺ T cells.

What are the six main antibody effector functions?

1. Opsonization

2. Complement activation

3. Immobilization

4. Cross-linking

5. ADCC

6. Neutralization.

What is opsonization?

Antibodies coat antigens, making them easier for phagocytes to engulf via Fc receptors.

How do antibodies activate complement?

Through the classical pathway, leading to C3b opsonization, inflammation, and MAC formation.

How do antibodies immobilize pathogens?

By binding flagella or pili, preventing movement or adherence.

What is cross-linking?

Binding identical epitopes on different antigens to form immune complexes cleared by phagocytes.

What is ADCC (Antibody-Dependent Cellular Cytotoxicity)?

NK cells bind Fc regions of antibodies on infected cells and trigger apoptosis.

What is neutralization?

Antibodies block pathogens or toxins from binding to host cells.