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Front. Immunol. | doi: 10.3389/fimmu.2018.02545

Identification of CVID patients with defects in immune repertoire formation or specification

  • 1Erasmus Medical Center, Erasmus University Rotterdam, Netherlands
  • 2University of Oxford, United Kingdom
  • 3Immunology, Leiden University Medical Center, Netherlands

.Common variable immune deficiency disorder (CVID) is the most clinically relevant cause of antibody failure. It is a highly heterogeneous disease with different underlying aetiologies. CVID has been associated with a quantitative B cell defect, however, little is known about the quality of B cells present. Here, we studied the naïve and antigen selected B-cell receptor (BCR) repertoire in 33 CVID patients using next generation sequencing, to investigate B cells quality. Analysis for each individual patient revealed whether they have a defect in immune repertoire formation (V(D)J recombination) or specification (somatic hypermutation, subclass distribution or selection).
The naïve BCR repertoire was normal in most of the patients, although alterations in repertoire diversity and the junctions were found in a limited number of patients indicating possible defects in early B-cell development or V(D)J recombination in these patients. In contrast, major differences were found in the antigen selected BCR repertoire. Here, most patients (15/17) showed a reduced frequency of somatic hypermutation (SHM), changes in subclass distribution and/or minor alterations in antigen selection.
Together these data show that in our CVID cohort only a small number of patients have a defect in formation of the naïve BCR repertoire, whereas the clear majority of patients have disturbances in their antigen selected repertoire, suggesting a defect in repertoire specification in the germinal centres of these patients. This highlights that CVID patients not only have a quantitative B cell defect, but that also the quality of, especially post germinal centre B cells, is impaired.

Keywords: Common Variable Immune Deficiencies, B-cell receptor, IGH repertoire, repertoire specification, Repertoire formation

Received: 13 Aug 2018; Accepted: 16 Oct 2018.

Edited by:

Guzide Aksu, Ege University, Turkey

Reviewed by:

Claude-Agnes Reynaud, Institut National de la Santé et de la Recherche Médicale (INSERM), France
Bhargavi Duvvuri, University of Washington, United States  

Copyright: © 2018 van Schouwenburg, IJspeert, Pico-Knijnenburg, Dalm, van Hagen, van Zessen, Stubbs, Patel and van der Burg. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Mirjam van der Burg, Leiden University Medical Center, Immunology, Leiden, 3015 GE, Netherlands, m.van_der_burg@lumc.nl