CD21 and CD19 deficiency: Two defects in the same complex leading to different disease modalities.
OBJECTIVE
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.
Dept. of Immunology, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80 3015 CN, Rotterdam, The Netherlands.
Marjolein W J
MW
Wentink
Dept. of Laboratory Medicine, Medical Immunology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
Annechien J A
AJ
Lambeck
Dept. of Immunology, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80 3015 CN, Rotterdam, The Netherlands.
Menno C
MC
van Zelm
Dept. of Immunology, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80 3015 CN, Rotterdam, The Netherlands.
Erik
E
Simons
Dept. of Immunology, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80 3015 CN, Rotterdam, The Netherlands.
Jacques J M
JJ
van Dongen
Dept. of Immunology, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80 3015 CN, Rotterdam, The Netherlands.
Hanna
H
IJspeert
Dept. of Pediatrics, Beatrix Children's Hospital, University of Groningen, University Medical Centre Groningen, Hanzeplein 1,9700 RB, Groningen, The Netherlands.
Elisabeth H
EH
Schölvinck
Dept. of Immunology, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80 3015 CN, Rotterdam, The Netherlands. Electronic address: m.vanderburg@erasmusmc.nl.
Mirjam
M
van der Burg
D000293:Adolescent; D000361:Agammaglobulinemia / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D016130:Immunophenotyping; D008297:Male; D009154:Mutation / Q000276:immunology; D017464:Receptors, Complement 3d / Q000172:deficiency* / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
D018941:Antigens, CD19; D017464:Receptors, Complement 3d
CD19; CD21; CD81; Hypogammaglobulinemia; Primary antibody deficiency