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USMLE Step 1ImmunologyEP 04 of 14

Antibody isotypes and class switching

Every antibody class has one main job. A B cell can change its class without changing what it recognises, and the helper T cell and the enzyme AID decide how.

  • 5:13 video
  • 3 min read
  • 15 sources
  • Published 15 Nov 2026
Video lesson · 5:13 · Watch on YouTubeSeries: Immunology · @medservatory
Chapters (11)
By the end of this lesson

Describe the function of each antibody class (IgM, IgD, IgG, IgA, IgE) and explain how class switching, driven by CD40 ligand, CD40, cytokines and AID, changes the class but not the antigen specificity.

The short version

  1. Switching swaps the constant region of the heavy chain and never the variable region, so specificity is kept.
  2. Class switching needs CD40 ligand on the helper T cell binding CD40 on the B cell, cytokines, and the enzyme AID.
  3. Cytokines choose the class: interleukin-4 toward IgE, transforming growth factor beta toward IgA, interferon gamma toward IgG.
  4. IgM comes first and is secreted as a pentamer; IgG is the most abundant and the only class that crosses the placenta.
  5. IgA guards mucosal surfaces as a secretory dimer; IgE arms mast cells and basophils.

The puzzle: antibodies the baby never made

A healthy newborn has antibodies in the blood that the baby never made. They are the mother's, and they crossed the placenta. But the mother's IgM did not.[1][9]

So why only one class? This lesson on antibody isotypes and class switching covers each class's job and how a B cell chooses its class. The puzzle is solved at the end.

Variable and constant regions: what defines an antibody class

Every antibody is a Y. The arm tips, the variable region, bind the antigen. The stem, the constant region of the heavy chain, sets the class, also called the isotype.[1][2]

The five classes are IgM, IgD, IgG, IgA and IgE. A naive B cell wears IgM and IgD on its surface as its receptor, both with the same specificity. Only a trace of IgD circulates in serum.[2][15]

How class switching works: T-cell help, CD40 ligand and AID

Class switching changes the constant region and keeps the variable region, so antigen specificity is kept.[3][4]

  1. The B cell presents peptideIn a protein response, the B cell presents peptide on MHC class II.[3]
  2. A helper T cell recognises itThe helper T cell recognises that peptide–MHC class II complex.[3]
  3. The T cell gives two thingsCD40 ligand, which binds CD40 on the B cell, and cytokines.[3][4]
  4. AID cuts the DNAActivation-induced cytidine deaminase (AID) damages the switch regions of the DNA, the stretch between is cut out, and a new constant gene is joined to the same variable gene.[3][4]

Cytokines choose the class

Which cytokine pushes the B cell toward which class
CytokinePushes toward
Interleukin-4IgE
Transforming growth factor betaIgA
Interferon gammaIgG

CD40 ligand with CD40 and AID make switching possible[3][4]; the cytokines decide where it goes.[5][6][7]

Primary and secondary antibody response

After a first exposure comes a lag of about ten days. IgM peaks near fourteen days, and then IgG takes over. On re-exposure the response is faster and bigger, and mostly IgG.[1][2]

Primary response timeline
  1. Day 0: first exposure
  2. About day 10: the lag ends and antibody appears
  3. About day 14: IgM peaks
  4. After that: IgG takes over

What each antibody class does: IgM, IgG, IgA, IgE and IgD

One main job per class
ClassForm and main job
IgMFirst antibody made. Secreted as a pentamer held by a J chain, with ten binding sites, so it clumps microbes and activates complement.[8]
IgGMost abundant, about 80% of serum antibody. Opsonizes, neutralizes and activates complement. The only class that crosses the placenta.[1][9]
IgAGuards the mucosa. Secreted as a dimer with a J chain and a secretory component, in mucus, tears, saliva and breast milk, where it traps pathogens.[1][10]
IgEThe rarest class. Its tail binds mast cells and basophils, which release mediators when antigen cross-links the bound IgE: defence against parasites, and allergy.[1][11]
IgDCo-expressed with IgM on the naive B cell as its receptor; only a trace circulates.[2][15]

IgM's pentamer gives it ten antigen-binding sites. That is why it is so good at clumping microbes and activating complement.[8]

The newborn puzzle, solved

The newborn's antibodies were IgG, the one class that crosses the placenta. The mother's IgM, a large pentamer, did not cross.[1][9]

Practice question

Original · USMLE style
Your turnQB-MS-S1-IMM-011-01

A 5-year-old boy has recurrent sinus and lung infections. Physical examination shows cervical lymphadenopathy. A lymph node biopsy shows markedly enlarged germinal centres. Serum IgM is markedly elevated, while IgG, IgA and IgE are very low. Flow cytometry shows normal numbers of B cells and T cells.

Deficiency of which of the following is most likely in this patient?
Pick one option. Your answers stay on this device.

Common questions

What is the difference between an antibody's variable and constant regions?

The variable region, at the arm tips, binds the antigen. The constant region of the heavy chain, the stem, sets the class.[1][2]

What does class switching change?

It changes the constant region of the heavy chain and keeps the variable region, so the antibody recognises the same antigen but belongs to a different class.[3]

What does a helper T cell provide for class switching?

CD40 ligand, which binds CD40 on the B cell, and cytokines. The enzyme AID then cuts and rejoins the DNA.[3][4]

Which antibody class crosses the placenta?

IgG is the only class that crosses the placenta.[1][9]

Which cytokines drive switching to IgE, IgA and IgG?

Interleukin-4 pushes toward IgE, transforming growth factor beta toward IgA, and interferon gamma toward IgG.[5][6][7]

Transcript

Read the full narration, by chapter685 words

0:00The puzzle: a newborn with antibodies it never made

A healthy newborn has antibodies in the blood that the baby never made. They are the mother's, and they crossed the placenta. But the mother's I g M did not. Why only one class? And how does a B cell choose its class? Today: each class's job, and how a B cell switches.

0:20Every antibody is a Y: variable vs constant region, five classes, the naive B cell

Every antibody is a Y. The arm tips, the variable region, bind the antigen. The stem, the constant region of the heavy chain, sets the class. The five classes are I g M, I g D, I g G, I g A and I g E. A naive B cell wears I g M and I g D on its surface as its receptor, both with the same specificity; only a trace of I g D circulates.

0:50Class switching: T-cell help, CD40L with CD40, AID

Class switching changes the constant region and keeps the variable region, so specificity is kept. In a protein response, the B cell presents peptide on MHC class two, and a helper T cell recognises it. The T cell then gives two things: CD 40 ligand, which binds CD 40 on the B cell, and cytokines. The enzyme activation-induced cytidine deaminase, AID, damages the switch regions of the DNA, the stretch between is cut out, and a new constant gene is joined to the same variable gene.

1:27Cytokines choose the class: IL-4, TGF-beta, interferon gamma

The cytokines choose the class. Interleukin four pushes toward I g E, transforming growth factor beta toward I g A, and interferon gamma toward

1:40Primary vs secondary response: the lag, IgM then IgG

I g G. After a first exposure comes about 10 days of lag, then I g M peaks near 14 days, then I g G takes over. On re-exposure the response is faster and bigger, and mostly I g G. I g M comes first.

1:56IgM: first and pentameric

Secreted I g M is a pentamer held by a J chain, with 10 binding sites, so it clumps microbes and activates complement.

2:07IgG: most abundant, the one class that crosses the placenta

I g G is the most abundant, about 80% of serum antibody. It opsonizes, neutralizes, activates complement, and is the only class that crosses the placenta.

2:19IgA and IgE: mucosal guard and mast-cell arming, and the newborn solved

I g A guards the mucosa. A dimer with a J chain and a secretory component, it sits in mucus, tears, saliva and breast milk, and traps pathogens. I g E is the rarest. Its tail binds mast cells and basophils, which release mediators when antigen bridges it: defence against parasites, and allergy. So the newborn's antibodies were I g G, the one class that crosses.

2:50Practice question

Your turn. A 5-year-old boy has recurrent sinus and lung infections. He has cervical lymphadenopathy, and a lymph node biopsy shows markedly enlarged germinal centres. Serum I g M is markedly elevated, while I g G, I g A and I g E are very low. Flow cytometry shows normal B cells and T cells. Deficiency of which of the following is most likely? A, activation-induced cytidine deaminase. B, CD 40 ligand on activated T cells. C, CD 40 on B cells and dendritic cells. D, Bruton tyrosine kinase protein. E, recombination-activating gene one protein. Pause here and decide. B is out: CD 40 ligand deficiency looks

3:44Answer: why B, C, D and E are out

similar, but it leaves no germinal centres, and his are swollen. C is out: CD 40 deficiency also prevents germinal centres from forming. D is out: Bruton tyrosine kinase deficiency leaves almost no B cells, with every class low. E is out: recombination-activating gene one starts VDJ recombination; its loss blocks B and T cell development, which are normal here. So the answer is A. Without AID the B cell cannot switch, so I g M piles up, I g G, I g A and I g E stay low, and the germinal centres swell.

4:31Recap and next lesson

Three things to keep. One: switching swaps the constant region, never the variable region, and needs CD 40 ligand with CD 40, plus AID. Two: cytokines choose the class: interleukin four for I g E, transforming growth factor beta for I g A, interferon gamma for I g G. Three: I g M first and pentameric, I g G crosses the placenta, I g A guards mucosa, I g E arms mast cells. Next, hypersensitivity: how these antibodies and T cells cause disease.

Sources

Numbers in the text, e.g. [1], point here
  1. OpenStax Microbiology, 18.1 Overview of Specific Adaptive Immunity. openstax.org/books/microbiology/pages/18-1-overview-of-specific-adaptive-immunity
  2. OpenStax Microbiology, 18.4 B Lymphocytes and Humoral Immunity. openstax.org/books/microbiology/pages/18-4-b-lymphocytes-and-humoral-immunity
  3. Durandy A, et al. Class switch recombination and somatic hypermutation in the germinal centre (2013). europepmc.org/article/PMC/PMC3580555
  4. Europe PMC PMC11322596 (CD40-CD40L signalling and class switching defects). europepmc.org/article/PMC/PMC11322596
  5. Snapper CM, et al. IL-4 and switching to IgE (1988). europepmc.org/article/PMC/PMC2189023
  6. Europe PMC PMC7097243 (TGF-beta and IgA). europepmc.org/article/PMC/PMC7097243
  7. Europe PMC PMC7663252 and PMC12563229 (cytokines and class choice, including interferon gamma toward IgG). europepmc.org/article/PMC/PMC7663252 · europepmc.org/article/PMC/PMC12563229
  8. Europe PMC PMC7709107 (IgM pentamer, J chain, avidity, complement). europepmc.org/article/PMC/PMC7709107
  9. Europe PMC PMC6963682 (IgG and FcRn across the placenta). europepmc.org/article/PMC/PMC6963682
  10. Europe PMC PMC3709412 (secretory IgA). europepmc.org/article/PMC/PMC3709412
  11. Europe PMC PMC6640697 (IgE, mast cells and basophils). europepmc.org/article/PMC/PMC6640697
  12. Europe PMC PMC6168630 (AID deficiency, autosomal recessive hyper-IgM). europepmc.org/article/PMC/PMC6168630
  13. Europe PMC PMC2424073 and PMC13177434 (X-linked agammaglobulinaemia, BTK). europepmc.org/article/PMC/PMC2424073 · europepmc.org/article/PMC/PMC13177434
  14. Europe PMC PMC212695 and PMC12829761 (RAG1 and V(D)J recombination; IUIS 2024 classification). europepmc.org/article/PMC/PMC212695 · europepmc.org/article/PMC/PMC12829761
  15. Wikipedia (secondary, for tables): Immunoglobulin D, Immunoglobulin class switching and Hyper-IgM syndrome. en.wikipedia.org/wiki/Immunoglobulin_D · en.wikipedia.org/wiki/Immunoglobulin_class_switching · en.wikipedia.org/wiki/Hyper-IgM_syndrome

The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.

Image credits. Illustrations: Servier Medical Art (smart.servier.com), CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), recoloured, outlined and cropped: "IgM", "Placenta", "Baby girl (new-born baby)", "Breast", "Lymph node". Germinal center icon by El-Jayawant and mast cell degranulation icon by Sebastian Reinig, via bioicons.com, CC BY 4.0, adapted (recoloured, cropped). B cell: NIAID NIH BioArt (bioart.niaid.nih.gov/bioart/612), public domain. Original diagrams: the antibody Y and the five-class row, the class-switch DNA strip, the CD40L-CD40 contact, the cytokine arrows, the primary and secondary response curve, the secretory IgA dimer and the immunoglobulin bar strip (schematic, not to scale). No AI-generated teaching images.

Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-IMM-011.

For exam study only, not medical advice. Read the medical disclaimer.

In this series

Playlist on YouTube
← Previous · EP 03Th1, Th2, Th17 and Treg: helper T-cell subsets
  1. EP 01MHC I vs MHC II: how antigen presentation works5:03
  2. EP 02T-cell activation: the two-signal model4:58
  3. EP 03Th1, Th2, Th17 and Treg: helper T-cell subsets5:13
  4. EP 04Antibody isotypes and class switching5:13
  5. EP 05Central vs peripheral tolerance: how lymphocytes learn self-tolerance5:26
  6. EP 06Complement system explained: three pathways, one ending5:24
  7. EP 07Complement deficiencies: C1q, C3, C5–C9 and C1 inhibitor5:15
  8. EP 08Hypersensitivity types I to IV: the four effectors5:20
  9. EP 09B-cell vs T-cell immunodeficiency: predict the infections5:24
  10. EP 10Hyper IgM syndrome: CD40 ligand and class switching5:19
  11. EP 11Chronic granulomatous disease: NADPH oxidase and the respiratory burst5:20
  12. EP 12Leukocyte adhesion deficiency: CD18 and neutrophil extravasation5:01
  13. EP 13Transplant rejection explained: hyperacute, acute, chronic and GVHD5:51
  14. EP 14Vaccine types explained: live, inactivated, conjugate and mRNA5:41