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

•CD21 deficiency leads to a less severe clinical phenotype than CD19 deficiency.•Upon in vitro stimulation CD21−/− B cells respond like normal B cells.•Upon in vitro stimulation CD19−/− B cells show a severely reduced response.•Affinity maturation is less affected by CD21 deficiency than by CD19 deficiency.

PurposeDeficiencies in CD19 and CD81 (forming the CD19-complex with CD21 and CD225) cause a severe clinical phenotype. One CD21 deficient patient has been described. We present a second CD21 deficient patient, with a mild clinical phenotype and compared the immunobiological characteristics of CD21 and CD19 deficiency.MethodsCD21 deficiency was characterized by flowcytometric immunophenotyping and sequencing. Real-time PCR, in vitro stimulation and next generation sequencing were used to characterize B-cell responses and affinity maturation in CD21−/− and CD19−/− B cells.ResultsA compound heterozygous mutation in CD21 caused CD21 deficiency. CD21−/− B cells responded normally to in vitro stimulation and AID was transcribed. Affinity maturation was less affected by CD21 than by CD19 deficiency.ConclusionsBoth CD21 and CD19 deficiencies cause hypogammaglobulinemia and reduced memory B cells. CD19 deficiency causes a more severe clinical phenotype. B-cell characteristics reflect this, both after in vitro stimulation as in affinity maturation.