B Lymphocytes
Development — two stages, two places ★★★
B-cell development splits cleanly in two, and the dividing line is antigen. The antigen-independent stage happens in the bone marrow, before the cell has ever met a foreign molecule — this is where the receptor is built and self-tolerance imposed. The antigen-dependent stage happens in the peripheral immune organs, and only begins when antigen arrives.
| Stage | Surface immunoglobulin | What happens |
|---|---|---|
| Pro-B cell | — | Begins to express Igα / Igβ (CD79a/CD79b) |
| Pre-B cell | pre-BCR | Expresses the pre-BCR |
| Immature B cell | mIgM | Expresses a complete BCR |
| Mature / naïve B cell | mIgM and mIgD | Leaves the marrow; the co-expression is the marker of maturation |
| Plasma cell | No mIg at all | Secretes antibody instead |
When a B cell becomes a plasma cell it does not invent a new protein. It secretes a modified version of its own B-cell receptor — and the BCR and the resulting antibody have identical antigen specificity. That is clonal selection made physical: the receptor that happened to fit the antigen becomes, without redesign, the soluble weapon aimed at it. It is also why Unit 3's distinction holds — membrane Ig and secreted Ig are two forms of one molecule.
- Where does the antigen-independent stage occur? → Bone marrow
- Name the four bone-marrow stages. → Pro-B → pre-B → immature B → mature/naïve B
- What do pro-B cells first express? → Igα/Igβ (CD79a/CD79b)
- What marks an immature B cell? → mIgM alone
- What marks a mature B cell? → mIgM and mIgD together
- What surface Ig does a plasma cell carry? → None
Central tolerance — three ways to deal with self-reactivity ★★
T cells in Unit 7 had one answer to self-reactivity: delete it. B cells have three, and the middle one is the interesting one, because it is the only place in immunology where a cell gets a second attempt at its own receptor.
| Mechanism | What happens |
|---|---|
| 1 · Clonal deletion | The self-reactive immature B cell dies by apoptosis |
| 2 · Receptor editing | The cell rearranges its light-chain gene again, producing a new receptor with a different specificity — a second chance rather than death |
| 3 · Anergy | The cell survives and migrates to the periphery, but is functionally unresponsive |
It is worth asking why the immune system bothers. Making a lymphocyte is expensive, and a B cell that is self-reactive is usually so because of one unlucky chain, not because the whole cell is wrong. Re-rearranging the light chain salvages the investment. T cells have no equivalent, because their restriction to self-MHC has to be established first and cannot be re-rolled without breaking it. So the B cell — which does not need MHC restriction — can afford a second attempt that the T cell cannot.
- Name the three mechanisms of B-cell central tolerance. → Clonal deletion, receptor editing, anergy
- What is receptor editing? → Re-rearrangement of the light-chain gene to give a new, non-self-reactive specificity
- What happens to an anergic B cell? → It survives and migrates to the periphery but is unresponsive
The BCR complex ★★★
The BCR has exactly the same architecture problem as the TCR in Unit 7, and exactly the same solution. Membrane immunoglobulin binds antigen beautifully but cannot signal, so it is paired with an invariant partner that can.
| Component | Role |
|---|---|
| BCR — membrane-associated Ig (mIg) | Antigen binding, through VH + VL — the same six CDRs as Unit 3 |
| Igα (CD79a) / Igβ (CD79b) | Signal transduction — bind mIg and transduce signals into the B cell, through ITAM motifs |
T cell: TCR binds, CD3 signals — via ITAM.
B cell: mIg binds, Igα/Igβ signals — via ITAM.
One pattern, two receptors. If you can state it for one, you can state it for the other.
- What are the two parts of the BCR complex? → Membrane Ig, and Igα/Igβ (CD79a/CD79b)
- Which part binds antigen? → The mIg, via VH + VL
- Which part signals, and how? → Igα/Igβ, via ITAM motifs
- What is the T-cell equivalent of Igα/Igβ? → CD3
The B-cell co-receptor ★★★
A complex of CD19, CD21 and CD81, which enhances the ability of naïve B cells to respond to antigen and transduces the first signal together with Igα/Igβ. CD21 is CR2, the C3d receptor — and the Epstein–Barr virus receptor.
CD21 binds C3d — a complement fragment. So if an antigen has already been tagged by complement, the B cell engages it through both the BCR and the co-receptor at once, and the activation threshold falls dramatically.
That is the join between Unit 4 and this one. Complement does not merely kill things — it marks antigen as worth responding to, and the B cell reads that mark. Innate immunity is, quite literally, vouching for the antigen.
It also explains a piece of clinical trivia that is not trivia at all: EBV infects B cells because it uses CD21 as its way in. The virus has found the one receptor that guarantees entry to the cell type it wants.
- Name the three components of the B-cell co-receptor. → CD19, CD21, CD81
- What does it do? → Enhances naïve B-cell responsiveness and helps transduce signal 1
- What does CD21 bind? → C3d — it is CR2 — and it is the EBV receptor
- Is CD20 part of the co-receptor? → No. That is the trap in True/False Q2
Two signals for B-cell activation ★★★
| Signal | Delivered by |
|---|---|
| Signal 1 — the BCR signal | BCR complex binding antigen, with CD19/CD21/CD81 as co-receptor |
| Signal 2 — the co-stimulatory signal | CD40 on the B cell binding CD40L on the activated Th cell |
The other co-stimulatory molecules on B cells are B7-1 (CD80) and B7-2 (CD86) — but note which way these point. They are expressed on professional APCs (DC, macrophage, B cell) and their ligands are CD28 and CTLA-4 on T cells. So B7 on the B cell is not a signal to the B cell; it is the B cell giving signal 2 to a T cell. Their expression is increased by microbial products such as LPS, by cytokines such as IFN-γ, and by CD40 binding CD40L. Adhesion molecules — ICAM-1 (CD54) and LFA-1 — complete the contact.
Put §5 next to Unit 7 §5 and the reciprocity becomes obvious. The B cell presents antigen on MHC II and offers B7, giving the T cell its signal 2 through CD28. The activated T cell then puts CD40L on its surface and gives the B cell its signal 2 through CD40.
Neither cell can finish the job alone, and each supplies the other's licence. That mutual dependence is the mechanism behind everything Unit 2 said about TD antigens — why a protein antigen needs T help, why class switching and memory follow, and why conjugating a polysaccharide to a protein carrier transforms a vaccine.
- What are the two signals for B-cell activation? → BCR + antigen with the co-receptor; CD40 with CD40L
- Which molecule on the B cell gives the key second signal? → CD40 — this is MCQ Q10
- Which cell carries CD40L? → The activated Th cell
- What do B7-1 and B7-2 on a B cell do? → Give signal 2 to the T cell, via CD28
- What increases B7 expression? → LPS, IFN-γ, and CD40–CD40L binding
Other surface molecules ★★★
| Molecule | Role |
|---|---|
| CD19 | A specific marker of the B-cell surface; part of the co-receptor; a target of immunotherapy for B-cell leukaemia |
| CD20 | A B-cell-specific marker; the target molecule recognised by therapeutic monoclonal antibody |
| CD22 | Carries an ITIM in its cytoplasmic tail; negatively regulates the CD19/CD21/CD81 co-receptor |
| CD32 | Negative regulation of B-cell activation and antibody secretion (the IgG Fc receptor from Unit 6) |
| Mitogen receptors | PWM-R (pokeweed), LPS-R (mouse), SPA-R (staphylococcal protein A) |
These are not academic markers. Rituximab is an anti-CD20 monoclonal antibody that depletes B cells, and it treats B-cell lymphoma, rheumatoid arthritis and several autoimmune diseases. CD19 is the target of CAR-T therapy — a patient's own T cells engineered to carry an anti-CD19 receptor, which has produced remissions in refractory B-cell leukaemia that nothing else could touch.
Both work for the same reason: the marker is on every B cell of the lineage, including the malignant ones, and on nothing else. You meet both drugs again in Unit 17.
- Which molecule is expressed on B cells: CD2, CD3, CD20 or PD-1? → CD20 — this is MCQ Q12
- What is CD19, and why does it matter clinically? → A B-cell-specific marker and co-receptor component; the CAR-T target
- What does CD22 do? → Carries an ITIM and negatively regulates the co-receptor
- What does CD32 do on B cells? → Negatively regulates activation and antibody secretion
B1 and B2 cells ★★
| B1 cells | B2 cells (conventional) | |
|---|---|---|
| Class | Innate immune cells | Adaptive immune cells |
| Proportion | 5–10% of B cells | The majority |
| Origin | Fetal liver; capable of self-renewal | Appears late in ontogeny |
| Location | Peritoneal cavity, pleural cavity, intestinal mucosal lamina propria | Peripheral lymphoid organs |
| Antigen spectrum | Narrow — mainly TI antigens and autoantigens | Broad — mainly TD antigens |
| T-cell help | Not required | Required |
| Class switching | None | Yes |
| Memory | None — no secondary response | Yes |
| Antibody | Low-affinity IgM, multi-reactive; spontaneous natural antibody against microbial LPS | High-affinity, mainly IgG |
| Also | Can cause autoimmune disease by producing pathogenic autoantibodies | Presents antigen, secretes cytokines, immune regulation |
Compare that B1 column with Unit 2's TI-antigen row and Unit 7's γδ T cell column: narrow repertoire, no T help needed, IgM only, no class switching, no memory, sitting at body surfaces. The same innate-lymphocyte pattern appears three times. It is why MCQ Q11 offers γδ T cells, B1 cells and NKT cells as distractors — they are the same kind of answer, and all three are wrong for the same reason.
The effector cell into which activated B cells differentiate. Plasma cells lose expression of surface immunoglobulin and become highly specialised for antibody secretion. They do not divide; some travel to the bone marrow and live for years, while others die within one or two weeks.
- B1 or B2 — which is innate? → B1
- Where do B1 cells sit? → Peritoneal cavity, pleural cavity, intestinal lamina propria
- Which antigens does each respond to? → B1 → TI antigens; B2 → TD antigens
- Which antibody does B1 make? → Low-affinity, multi-reactive IgM, with no class switching or memory
- What happens to surface Ig on a plasma cell? → It is lost — the cell secretes antibody instead
- Do plasma cells divide? → No
Functions of B lymphocytes ★★★
This section is Section V question 5 — 6 marks, set identically in both papers. TMU gives three headline functions, and the exam asks you to spread them across a list of specific roles. Learn the three headings first; the rest hangs off them.
1 · Production of antibody
- Neutralisation — recognise and specifically combine with antigen to neutralise toxin and block invasion by pathogens
- Activation of complement — the classical pathway (Unit 4)
- Fc-receptor binding — giving opsonisation, ADCC, and mediation of type I hypersensitivity by IgE
- Transport across placenta and mucosa — IgG through the placenta, sIgA to mucosal surfaces and through breast milk
2 · Antigen presentation to T cells
B cells are professional APCs. Antigen is recognised, concentrated and internalised by the BCR itself, or taken up by pinocytosis; after processing it is displayed as antigenic peptide–MHC class II and presented to Th cells. The deck adds the point that matters: this is especially important for soluble antigen, which macrophages and dendritic cells cannot capture efficiently.
A macrophage takes up whatever floats past. A B cell uses its antigen-specific receptor as the collecting tool — so it concentrates the one antigen it cares about, perhaps a thousand-fold, before presenting it. At low antigen concentrations, where a macrophage would capture almost nothing, the B cell specific for that antigen is still presenting it efficiently.
And it gets its reward immediately: the T cell it activates supplies CD40L back. The B cell presents antigen in order to obtain the help it needs to respond to that same antigen.
3 · Immune regulation
B cells secrete IL-6, IL-10 and TNF-α, regulating macrophages, dendritic cells, NK cells and T cells. There is also a suppressive subset — regulatory B cells (Breg) — which secrete IL-10, TGF-β and IL-35 and express FasL and PD-L1 to engage Fas and PD-1 on target cells. Bregs are implicated in autoimmune disease, transplantation, infection and tumour immunity.
Cellular response — B cells act as professional APCs, presenting peptide–MHC II to Th cells and thereby driving the cellular arm; they also secrete regulatory cytokines.
Humoral response — the central role: differentiate into plasma cells and secrete specific antibody.
Infection defence — antibody neutralises toxins and viruses, activates complement, and opsonises for phagocytosis; sIgA protects mucosa and IgG crosses the placenta to protect the newborn.
Hypersensitivity mediation — antibody mediates types I, II and III; IgE in particular drives type I.
Anti-tumour effect — antitumour antibody supports ADCC and complement-mediated lysis.
Allograft rejection — alloantibody contributes to rejection, particularly hyperacute and antibody-mediated rejection.
- Name the three functions of B cells. → Antibody production · antigen presentation to T cells · immune regulation
- Which cells can B cells present to, and on what? → Th cells, on MHC class II
- Why are B cells especially good at presenting soluble antigen? → The BCR concentrates it; macrophages and DCs cannot capture it efficiently
- Which cytokines do B cells secrete? → IL-6, IL-10, TNF-α
- What do Breg cells secrete? → IL-10, TGF-β, IL-35
Revision layer
The exam map — this is one of the two richest units in the subject
| Section | Item | From |
|---|---|---|
| III. MCQ Q10 | CD40 delivers the second signal of B-cell activation | §5 |
| III. MCQ Q12 | CD20 is expressed on B cells | §6 |
| IV. True/False Q2 | Co-receptor is CD19/CD21/CD81 — F as printed | §4 |
| IV. True/False Q6 | mIgM + mIgD marks B-cell maturation — T | §1 |
| V. Brief answer Q5 | ⭐ Functions of B cells — 6 marks | §8 |
CD19 — co-receptor, CAR-T target.
CD20 — B-cell marker, rituximab target. NOT co-receptor.
CD21 — co-receptor, C3d and EBV receptor.
CD40 — second signal, ligand CD40L on T cells.
Learn each with its job, not as a list. Every one of the four exam items in this unit is testing whether you can tell them apart.
The whole unit on one screen
| Question | Answer |
|---|---|
| Two developmental stages? | Antigen-independent (bone marrow); antigen-dependent (periphery) |
| Four marrow stages? | Pro-B → pre-B → immature B → mature B |
| Maturation marker? | mIgM + mIgD |
| Three tolerance mechanisms? | Clonal deletion · receptor editing · anergy |
| BCR complex? | mIg binds; Igα/Igβ (CD79a/b) signals via ITAM |
| Co-receptor? | CD19 / CD21 / CD81 |
| CD21 binds? | C3d — and it is the EBV receptor |
| Two signals? | BCR + antigen; CD40 + CD40L |
| CD20? | B-cell-specific marker; rituximab target; not co-receptor |
| CD22 / CD32? | Both negative regulators (CD22 via ITIM) |
| B1 vs B2? | Innate, TI antigens, IgM only, no memory / adaptive, TD antigens, IgG, memory |
| Plasma cell? | No surface Ig; does not divide; secretes antibody |
| Three functions? | Antibody · antigen presentation · immune regulation |
- Which molecule on B cells gives the second signal? → CD40
- Name the co-receptor components. → CD19, CD21, CD81 — not CD20
- What marks B-cell maturation? → Co-expression of mIgM and mIgD
- Name the three tolerance mechanisms. → Clonal deletion, receptor editing, anergy
- What signals for the BCR? → Igα/Igβ, via ITAM — the CD3 equivalent
- B1 cells: T help, class switching, memory? → None of the three
- Name the three functions of B cells. → Antibody production, antigen presentation, immune regulation
- Why are B cells good at presenting soluble antigen? → The BCR concentrates it specifically