title: B-cell maturation and antibody responses in individuals carrying a mutated CD19 allele.
abstract: Homozygous CD19 mutations lead to an antibody deficiency due to disruption of the CD19 complex and consequent impaired signaling by the B-cell antigen receptor. We studied the effects of heterozygous CD19 mutations on peripheral B-cell development and antibody responses in a large family with multiple consanguineous marriages. Sequence analysis of 96 family members revealed 30 carriers of the CD19 mutation. Lymphocyte subset counts were not significantly different between carriers and noncarriers in three different age groups (0-10 years; 11-18 years; adults). B cells of carriers had reduced CD19 and CD21 median expression levels, and had reduced proportions of transitional (0-10 years) and CD5(+) B cells (adults). CD19 carriers did not show clinical signs of immunodeficiency; they were well capable to produce normal serum Ig levels and had normal responses to primary and booster vaccinations. The frequency of mutated Vκ alleles was not affected. Heterozygous loss of CD19 causes some changes in the naive B-cell compartment, but overall in vivo B-cell maturation or humoral immunity is not affected. Many antibody deficiencies are not monogenetic, but likely caused by a combination of multiple genetic variations. Therefore, functional analyses of immune cell function should be carried out to show whether heterozygous mutations contribute to disease.
authors.affiliation: Department of Pediatric Immunology and Allergy, Selçuk University, Konya, Turkey.
authors.forename: H
authors.initials: H
authors.lastname: Artac
authors.forename: I
authors.initials: I
authors.lastname: Reisli
authors.forename: R
authors.initials: R
authors.lastname: Kara
authors.forename: I
authors.initials: I
authors.lastname: Pico-Knijnenburg
authors.forename: S
authors.initials: S
authors.lastname: Adin-Çinar
authors.forename: S
authors.initials: S
authors.lastname: Pekcan
authors.forename: C M
authors.initials: CM
authors.lastname: Jol-van der Zijde
authors.forename: M J D
authors.initials: MJ
authors.lastname: van Tol
authors.forename: L E
authors.initials: LE
authors.lastname: Bakker-Jonges
authors.forename: J J M
authors.initials: JJ
authors.lastname: van Dongen
authors.forename: M
authors.initials: M
authors.lastname: van der Burg
authors.forename: M C
authors.initials: MC
authors.lastname: van Zelm
mesh_terms: D000328:Adult; D000917:Antibody Formation / Q000235:genetics* / Q000276:immunology; D018941:Antigens, CD19 / Q000235:genetics*; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002648:Child; D015331:Cohort Studies; D003241:Consanguinity; D005260:Female; D006579:Heterozygote; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D009154:Mutation; D010375:Pedigree; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: D018941:Antigens, CD19; D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell