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.

CD19, CD21, CD81, Hypogammaglobulinemia, Primary antibody deficiency
dx.doi.org/10.1016/j.clim.2015.08.010, hdl.handle.net/1765/87899
Clinical Immunology
Department of Immunology

Wentink, M.W.J, Lambeck, A.J.A, van Zelm, M.C, Simons, E.J, van Dongen, J.J.M, IJspeert, H, … van der Burg, M. (2015). CD21 and CD19 deficiency: Two defects in the same complex leading to different disease modalities. Clinical Immunology, 161(2), 120–127. doi:10.1016/j.clim.2015.08.010