4. B cells and antibodies

K.P- 29/01/2026

What is the B cell receptor (BCR)?

The membrane-bound antibody on the surface of a B cell that recognises native antigen — it is highly specific and highly diverse. When the B cell becomes a plasma cell, the BCR is released as a soluble antibody

Where do B cells originate and mature?

B cells originate from haematopoietic stem cells in the bone marrow and undergo maturation there (unlike T cells, which mature in the thymus). They undergo gene rearrangement before leaving

What happens after a mature B cell leaves the bone marrow?

It circulates through the lymphatic system (e.g. lymph nodes, spleen) searching for its specific antigen. It will not be activated until it encounters that antigen — this prevents premature activation

What is the function of the lymph node?

It is a structured site for antigen presentation, lymphocyte interaction, and clonal selection, ensuring coordinated and antigen-specific adaptive immune responses

What is clonal selection?

The process by which only B cells that recognise their specific antigen are selected to proliferate. Only activated B cells can respond to IL-2 and divide, forming a clone of cells all with identical BCR

What is VDJ recombination?

The gene rearrangement process that occurs in the bone marrow before antigen is seen. Gene segments (V = variable, D = diversity, J = joining) are randomly combined to create a unique antigen-binding site for each B cell

Which chain undergoes rearrangement first in B cell development?

The heavy chain undergoes D-J then V-DJ rearrangement first. The light chain (V-J only) rearranges later, towards the end of the immature B cell's lifecycle

What are the two checkpoints in B cell gene rearrangement?

First checkpoint

What happens to B cells that react to self-antigens during development?

They are apoptosed (undergo programmed cell death) and phagocytosed by nearby dendritic cells and macrophages — this prevents autoimmunity

What is somatic hypermutation?

A process that occurs in the germinal centre after antigen stimulation, introducing random point mutations into the variable regions of the heavy (and sometimes light) chains to improve antigen binding. Only the variable region is affected

What is affinity maturation?

The process by which B cells with the highest affinity for their antigen are selected to survive, while lower-affinity B cells are apoptosed. It occurs in the germinal centre and is driven by somatic hypermutation

What are the possible fates of an activated B cell?

Apoptosis within hours (failed somatic hypermutation)

short-lived plasma blast during early infection

memory B cell surviving for decades

or long-lived plasma cell in bone marrow (can survive 40+ years after vaccination)

What is a plasma cell?

A terminally differentiated effector B cell specialised for high-rate antibody secretion. Plasma cells downregulate surface BCRs, lose the ability to respond to antigen, and can no longer undergo class-switch recombination or somatic hypermutation

What does differential RNA splicing do to allow antibody secretion?

It replaces the hydrophobic transmembrane sequence (which anchors the antibody to the B cell surface) with a hydrophilic sequence, allowing the antibody to be secreted rather than remaining membrane-bound

What is the general structure of an antibody?

Two identical heavy chains and two identical light chains (either lambda or kappa), joined by disulfide bonds. It has a variable region (antigen-binding) and a constant region (determines class/effector function), plus a hinge region giving flexibility

What are the Fab and Fc fragments?

Fab (Fragment antigen binding) — the two arms that bind antigen. Fc (Fragment crystallizable/constant) — the tail region that interacts with other parts of the immune system (e.g. macrophages, complement). Produced by papain digestion

What is the hinge region and why is it important?

A flexible region between the Fab arms and Fc region that allows the antibody to adopt different angles, enabling multiple antibodies to opsonise a pathogen and alert the immune system

What is the hypervariable (HV) region / CDR?

Complementarity-determining regions within the variable domain that form the actual antigen-binding site. There are 3 HV regions per V domain, and 12 CDRs per antibody (bivalent = 2 binding sites × 2 chains × 3 HV regions)

What is an epitope?

A small part of the antigen that the antibody actually binds to. Usually a carbohydrate or protein exposed on the pathogen surface. Can be linear or conformational (discontinuous)

What is isotype (class) switching?

A process where the constant region of the antibody is changed (e.g. from IgM to IgG, IgA or IgE) while the variable region — and therefore antigen specificity — stays the same. This gives different effector functions

What enzyme mediates class switch recombination and where does it occur?

Activation-induced cytidine deaminase (AID). It occurs primarily in germinal centres of lymph nodes during secondary immune responses

What is the difference between VDJ recombination and class switch recombination?

VDJ recombination

recombines the variable region

generates unique antigen-binding specificity for each B cell. Class switch recombination

occurs in germinal centres after antigen stimulation

recombines the constant region

same antigen binding but different effector function

How many antibody isotypes do humans have and what are they?

Five — IgM, IgD, IgG, IgA, and IgE

What is IgM and what is its key function?

A pentamer (5 Ig units joined by disulfide bonds and a J chain). The first antibody secreted in a primary immune response. Excellent at activating complement via the classical pathway due to its five Fc regions

What is IgD and what is its function?

A monomer found mainly on the surface of naive B cells (acts as BCR). Very low serum levels. Does not activate complement. Function not fully understood — thought to be involved in B cell activation alongside IgM

What is IgA and where is it found?

The most abundant antibody in the body. Found in mucosal surfaces (lungs, gut, nose, mouth) and in breast milk. Exists as a dimer at mucosal surfaces. Passive antibody — cannot fix complement. Protects against ingested and inhaled pathogens

What is IgG and what are its functions?

The most common serum antibody with four subclasses (IgG1-4). Functions include neutralising viruses, opsonisation, crossing the placenta to protect the foetus, and providing passive immunity (IVIG). Produced during secondary immune responses

What is IgE and what is its role?

A monomer associated with allergic reactions (hay fever, asthma, anaphylaxis). Binds to mast cells — when allergen binds IgE, mast cells degranulate and release histamine, causing inflammation. Can be fatal in anaphylactic shock

What are the three main effector functions of antibodies?

Neutralisation (blocking pathogen/toxin binding to host cells)

opsonisation (coating pathogen to make it a target for phagocytosis by macrophages)

complement activation (classical pathway leading to lysis and inflammation)

What determines the isotype/class of an antibody?

The structure of the heavy chain constant region. The variable region determines antigen specificity

the constant region determines the antibody class and its effector functions

What is the role of IL-2 in B cell activation?

IL-2 (released from T helper cells) binds to the IL-2 receptor on activated B cells, promoting B cell proliferation. Naïve B cells do not express IL-2R, so only activated B cells can respond and divide

Why do approximately 90% of B cells that undergo gene rearrangement undergo apoptosis?

Because the rearrangement is random and many fail to produce a functional receptor, or the resulting BCR reacts to self-antigens (autoreactivity). Strict checkpoints eliminate non-functional or autoreactive cells

What is the germinal centre and why is it important?

A specialised structure within secondary lymphoid organs (e.g. lymph nodes) where activated B cells undergo somatic hypermutation, affinity maturation, class switch recombination, and fate decisions (plasma cell vs memory cell