U01.02.031 Immunodeficiencies B-cell disorders

B-cell disorders are primary immunodeficiencies characterized by defective B-cell development, differentiation, or function, leading to recurrent infections and immune dysfunction. Understanding these conditions is critical for mastering immunology on the USMLE Step 1.

B-Cell Disorders

1. X-Linked (Bruton) Agammaglobulinemia

Key Feature	Details
Defect	Mutation in BTK (a tyrosine kinase gene), resulting in no B-cell maturation.
Inheritance	X-linked recessive (affects boys).
Clinical Presentation	– Recurrent bacterial and enteroviral infections after 6 months (loss of maternal IgG).
	– Absent/scanty lymph nodes and tonsils (due to lack of germinal centers).
Laboratory Findings	– Absent B cells in peripheral blood.
	– Markedly reduced immunoglobulin (Ig) levels of all classes.
Management	– Live vaccines are contraindicated.

2. Selective IgA Deficiency

Key Feature	Details
Cause	Unknown.
Epidemiology	Most common primary immunodeficiency.
Clinical Presentation	– Asymptomatic in the majority of cases.
	– Increased susceptibility to airway and GI infections.
	– Associated with autoimmune diseases, atopy, and anaphylaxis to IgA-containing products.
Laboratory Findings	– Low IgA levels with normal IgG and IgM levels.
	– Increased susceptibility to giardiasis.
	– May cause false-positive β-hCG tests.

3. Common Variable Immunodeficiency (CVID)

Key Feature	Details
Defect	Impaired B-cell differentiation. Cause unknown in most cases.
Epidemiology	Can present in childhood but often diagnosed after puberty.
Clinical Presentation	– Increased risk of autoimmune disease, bronchiectasis, lymphoma, and sinopulmonary infections.
Laboratory Findings	– Decreased plasma cells.
	– Reduced immunoglobulin levels across all classes.

Points to Remember

Timing of Symptoms: B-cell disorders often manifest after 6 months due to the waning of maternal IgG.
Infection Types: Recurrent bacterial infections (especially encapsulated organisms) and susceptibility to specific viral and parasitic pathogens.
Contraindications: Live vaccines are unsafe in severe B-cell immunodeficiencies, such as X-linked agammaglobulinemia.
Laboratory Clues: Look for low immunoglobulin levels and absence of B cells in the peripheral blood in agammaglobulinemia.
Common Presentation: CVID presents later in life compared to other B-cell disorders.
Clinical Relevance: Always correlate immunodeficiency symptoms with specific defects and laboratory findings.

Study Tip

Create a comparison table summarizing the clinical, laboratory, and pathophysiological features of B-cell disorders to reinforce understanding and aid in differential diagnosis during the exam.

USMLE Step 1 Review Series

Curriculum