Adaptive Immunity II – B-Cell Receptor and Antibody Diversity

A set of vocabulary flashcards covering the genetic organization of immunoglobulin loci, mechanisms of B-cell receptor formation, and processes that generate antibody diversity.

Antibody Repertoire

The total number of different antibody specificities an individual can produce (~10⁸).

Immunoglobulin (Ig) Locus

Genomic region containing clustered V, (D), J, and C gene segments that encode antibody chains.

Heavy (H) Chain Locus

Ig locus on chromosome 14 that contains V, D, J, and multiple C gene segments (μ, δ, γ, ε, α).

Light (L) Chain Loci

Ig loci for κ (chromosome 2) and λ (chromosome 22) light chains, each with V, J, and C segments but no D segments.

Variable (V) Gene Segment

Segment that encodes most of the antibody variable region; selected during V-(D)-J recombination.

Diversity (D) Gene Segment

Short gene segment found only in heavy chains; contributes to variability of CDR3 when recombined.

Joining (J) Gene Segment

Segment that joins V (and D) segments to complete the variable region exon.

Constant (C) Gene Segment

Exon encoding the constant region that defines antibody class (isotype).

V-(D)-J Recombination

Somatic DNA rearrangement process that assembles one V, (one D), and one J segment to form an antibody variable-region exon.

Combinatorial Diversity

Antibody variability generated by different combinations of V, D, and J gene segments in heavy and light chains.

Junctional Diversity

Additional diversity created by imprecise joining, nucleotide additions, and deletions at V-D and D-J junctions.

Somatic Hypermutation (SHM)

AID-mediated point mutations in V-region genes of activated B cells, leading to affinity maturation.

Class-Switch Recombination (CSR)

DNA recombination replacing Cμ/Cδ with another heavy-chain C region (e.g., Cγ, Cα, Cε) without changing antigen specificity.

Activation-Induced Cytidine Deaminase (AID)

Enzyme that initiates both somatic hypermutation and class-switch recombination by deaminating cytidines in DNA.

Recombination Signal Sequence (RSS)

Conserved heptamer-spacer-nonamer motif flanking V, D, and J segments; guides V-(D)-J recombination.

12/23 Rule

Recombination occurs only between RSSs with 12-bp and 23-bp spacers, ensuring correct V-D-J assembly.

RAG-1 / RAG-2

Lymphoid-specific recombinase proteins that recognize RSSs and initiate double-strand DNA breaks during V-(D)-J recombination.

DNA-PK:Artemis Complex

Enzymatic pair that opens hairpin DNA ends and introduces variability during junction formation.

Terminal Deoxynucleotidyl Transferase (TdT)

Enzyme that randomly adds N-nucleotides to open DNA ends, increasing junctional diversity.

P Nucleotides

Short palindromic sequences generated when hairpin ends are asymmetrically cleaved during recombination.

N Nucleotides

Non-templated nucleotides added by TdT at V-D-J junctions, augmenting diversity of CDR3.

Complementarity Determining Region 3 (CDR3)

Most variable part of the antibody binding site, largely formed by V-D-J junctions.

Affinity Maturation

Selection of B cells producing higher-affinity antibodies after SHM during an immune response.

Isotype Switching

Synonym for class-switch recombination; changes antibody effector function while preserving specificity.

IgM

First antibody isotype expressed (membrane IgM) and secreted in primary immune responses; pentameric when secreted.

IgD

Isotype co-expressed with IgM on naïve mature B cells; function mainly as B-cell receptor.

Pro-B Cell

Early bone-marrow B-cell stage where heavy-chain D-J (then V-DJ) recombination occurs.

Pre-B Cell

Stage expressing μ heavy chain with surrogate light chain as the pre-B-cell receptor; light-chain V-J recombination begins.

Immature B Cell

B cell expressing surface IgM; undergoes central tolerance testing in bone marrow/spleen.

Mature (Naïve) B Cell

B cell expressing both IgM and IgD BCRs; circulates peripheral lymphoid organs awaiting antigen.

Plasma Cell

Antibody-secreting effector cell derived from activated B cells; lacks surface BCR and is usually short-lived.

Memory B Cell

Long-lived B cell formed after activation; rapidly mounts secondary responses upon re-encountering antigen.

Clonal Deletion

Apoptotic elimination of developing B cells that strongly bind self-antigen; central or peripheral tolerance mechanism.

T Helper (TH) Cytokines

Signals from CD4⁺ T cells that drive B-cell proliferation, SHM, and class switching to specific isotypes.

Autoimmune Disease

Pathology arising when tolerance fails and antibodies/BCRs attack self molecules (e.g., insulin in type 1 diabetes).