Antibody Gene Recombination and Hypermutation

What are the two main genetic mechanisms generating antibody diversity?

Gene recombination and somatic hypermutation

Where does antibody gene recombination primarily occur?

In the bone marrow

What antibody chain types are present in IgG?

Heavy chains (HC) and Light chains (LC)

What are the segments of the heavy chain (HC)?

VH, CH1, CH2, CH3

What segments are present in the light chain (LC)?

Variable region (VL) and Constant region (CL - either kappa or lambda)

How many genes encode for the VL kappa region in the LC?

30 genes

How many joining (J) segments are involved in LC recombination?

5 J segments

What does "VJ recombination" specifically refer to?

Recombination of Variable (V) and Joining (J) segments in the light chain

What segments recombine in heavy-chain gene rearrangement?

Variable (V), Diversity (D), and Joining (J) segments (VDJ recombination)

Where does B-cell maturation primarily occur?

In the lymph nodes

What are the three main steps in B-cell maturation?

Isotype class switching, somatic hypermutation, and affinity maturation

Define somatic hypermutation

High-rate mutation occurring in variable regions of antibody genes in activated B-cells

What is affinity maturation?

Process where B-cells producing higher-affinity antibodies are selectively expanded

What regions of antibodies undergo hypermutation?

Hypervariable complementarity-determining regions (CDRs)

Which CDR is most variable and critical for antigen binding?

CDR3

How are hypervariable "N" regions generated in antibody genes?

By deleting a few bases and adding random nucleotides

What is the biological advantage of affinity maturation?

It produces antibodies with progressively higher affinity for antigens

What triggers the start of somatic hypermutation?

B-cell activation following initial antigen exposure

Where specifically in lymph nodes does somatic hypermutation occur?

In germinal centers

What happens to B-cells with low-affinity antibodies during affinity maturation?

They undergo apoptosis (cell death)

What factor determines the survival of B-cells during affinity maturation?

Their affinity for available pathogens (antigens)

What is clonal expansion in B-cells?

Rapid proliferation of activated B-cells after antigen exposure

What is class switching (isotype switching) in B-cells?

A process where B-cells change the antibody isotype (e.g., from IgM to IgG or IgA) produced

Why are antibody variable regions important?

They determine antigen specificity and binding

What provides the diversity in antibodies during initial development?

Gene recombination of V, D, and J segments

What provides additional diversity after antigen stimulation?

Somatic hypermutation in germinal centers

Define apoptosis

Programmed cell death; removes B-cells producing low-affinity antibodies

What part of the antibody specifically binds antigens?

The Fab region (fragment antigen-binding)

What does "hypermutation selection" mean?

B-cells with highest antigen affinity are preferentially expanded, others eliminated

How do mutations occur during somatic hypermutation?

Through random DNA replication errors during rapid B-cell division