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B-cell maturation and antibody responses in individuals carrying a mutated CD19 allele

Genes & Immunity volume 11, pages 523–530 (2010)Cite this article

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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.

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Acknowledgements

The authors are indebted to Mrs S Posthumus for technical support with the IgκREHMA assay and Professor H Hooijkaas and his colleagues from the immunodiagnostic laboratory at the Erasmus MC for technical support with anti-nuclear antibody testing. This work was supported by a grant from the Scientific and Technological Research Council of Turkey (TUBITAK) to H Artac, a VENI grant (916.56.107) from the Dutch Organization for Scientific Research (NWO/ZonMW) to M van der Burg, and a grant from the Erasmus University Rotterdam (EUR-Fellowship) to MC van Zelm.

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Authors and Affiliations

  1. Department of Pediatric Immunology and Allergy, Meram Medical Faculty, Selçuk University, Konya, Turkey

    H Artac, I Reisli, R Kara & S Pekcan

  2. Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

    I Pico-Knijnenburg, L E Bakker-Jonges, J J M van Dongen, M van der Burg & M C van Zelm

  3. Department of Immunology, Institute for Experimental Medicine (DETAE), Istanbul University, Istanbul, Turkey

    S Adin-Çinar

  4. Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands

    C M Jol-van der Zijde & M J D van Tol

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  1. H Artac
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Correspondence to M C van Zelm.

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Artac, H., Reisli, I., Kara, R. et al. B-cell maturation and antibody responses in individuals carrying a mutated CD19 allele. Genes Immun 11, 523–530 (2010). https://doi.org/10.1038/gene.2010.22

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