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

Clin Immunol. 2015 Dec;161(2):120-7. doi: 10.1016/j.clim.2015.08.010. Epub 2015 Aug 30.

Abstract

Purpose: Deficiencies 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.

Methods: CD21 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.

Results: A 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.

Conclusions: Both 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.

Keywords: CD19; CD21; CD81; Hypogammaglobulinemia; Primary antibody deficiency.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Agammaglobulinemia / immunology
  • Antigens, CD19 / immunology*
  • B-Lymphocytes / immunology
  • Case-Control Studies
  • Humans
  • Immunologic Deficiency Syndromes / immunology*
  • Immunologic Memory / immunology
  • Immunophenotyping
  • Male
  • Mutation / immunology
  • Receptors, Complement 3d / deficiency*
  • Receptors, Complement 3d / immunology*
  • Signal Transduction / immunology

Substances

  • Antigens, CD19
  • Receptors, Complement 3d