B-cells are responsible for producing antibodies, an essential component of the adaptive immune system. Abnormal B-cells lead to reduced immunoglobulins (antibodies), called hypogammaglobulinaemia.
B-cell disorders lead to a susceptibility to infections, particularly respiratory tract infections. Patients are notably susceptible to infections caused by encapsulated bacteria (e.g., Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis).
Selective IgA Deficiency
Selective IgA deficiency is the most common immunoglobulin deficiency. Patients have low IgA levels and normal IgG and IgM levels.
IgA is present in secretions of the mucous membranes, such as saliva, respiratory tract, gastrointestinal tract, tears and sweat. IgA protects these mucous membranes against infection.
Selective IgA deficiency causes mild immunodeficiency. Patients are often asymptomatic and never diagnosed. Patients may have a tendency to recurrent infections (e.g., respiratory infections) and autoimmune conditions.
TOM TIP: IgA deficiency is relevant when testing for coeliac disease. The blood tests for coeliac disease are the IgA version of anti-TTG or anti-EMA antibodies. When testing for these antibodies, it is also important to measure total immunoglobulin A levels. If the total IgA is low due to IgA deficiency, the coeliac test will be falsely negative. In this circumstance, you can test for the IgG version of anti-TTG or anti-EMA antibodies.
Common Variable Immunodeficiency
Common variable immunodeficiency is caused by defects in B-cell differentiation and function. The result is that:
- IgG is low
- IgA is often low
- IgM may be low or normal
Common variable immunodeficiency leads to:
- Recurrent respiratory tract infections
- Inability to develop immunity to infections or vaccinations
- Increased risk of autoimmune disorders (e.g., rheumatoid arthritis)
- Increased risk of certain cancers (e.g., non-Hodgkin lymphoma)
Management involves immunoglobulin infusions and treating infections and complications as they occur.
X-linked Agammaglobulinaemia
X-linked agammaglobulinaemia is also known as Bruton’s agammaglobulinaemia. It is an X-linked recessive condition characterised by abnormal B-cell development and deficiency in all immunoglobulin classes. It causes issues similar to those of common variable immunodeficiency, but more severe and with an earlier onset.
Immunoglobulin Class-Switch Recombination Deficiency
Immunoglobulin class-switch recombination deficiency (also known as Hyper-IgM syndrome) is a group of disorders in which B cells cannot switch from producing IgM to other immunoglobulin types (IgG, IgA, and IgE). This is most commonly caused by a defect in the interaction between T-cells and B-cells (e.g., CD40 ligand deficiency), which prevents normal antibody class switching. Patients have normal or elevated IgM levels, with low IgG and IgA levels.
It leads to recurrent infections, particularly respiratory infections, as well as opportunistic infections such as Pneumocystis jirovecii. Patients may also have failure to thrive and chronic diarrhoea.
Management involves immunoglobulin replacement therapy, prophylactic antibiotics and avoiding live vaccines. In severe cases, haematopoietic stem cell transplantation may be required.
Last updated April 2026
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