CD21 and CD19 deficiency: Two defects in the same complex leading to different disease modalities

Area of Science:

• Immunology
• Genetics

Background:

• CD19-complex proteins, including CD19, CD81, CD21, and CD225, are crucial for B-cell function.
• Deficiencies in CD19 and CD81 result in severe clinical phenotypes.
• Only one patient with CD21 deficiency has been previously documented.

Observation:

• A second patient with CD21 deficiency was identified, exhibiting a milder clinical phenotype.
• The immunobiological characteristics of CD21 and CD19 deficiencies were compared.
• Flow cytometry, sequencing, and real-time PCR were employed to analyze B-cell responses and affinity maturation.

Findings:

• A compound heterozygous mutation in the CD21 gene was identified as the cause of CD21 deficiency.
• CD21-deficient B cells demonstrated normal in vitro stimulation responses with normal AID transcription.
• Affinity maturation was found to be less impaired in CD21 deficiency compared to CD19 deficiency.

Implications:

• Both CD19 and CD21 deficiencies lead to hypogammaglobulinemia and a decrease in memory B cells.
• CD19 deficiency is associated with a more severe clinical presentation than CD21 deficiency.
• B-cell characteristics post-stimulation and in affinity maturation correlate with the clinical severity of CD19 and CD21 deficiencies.