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The defect in humoral immunity in patients with Nijmegen breakage syndrome is explained by defects in peripheral B lymphocyte maturation
Author(s) -
Piątosa Barbara,
van der Burg Mirjam,
Siewiera Katarzyna,
Pac Małgorzata,
van Dongen Jacques J. M.,
Langerak Anton W.,
Chrzanowska Krystyna H.,
Bernatowska Ewa
Publication year - 2012
Publication title -
cytometry part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.316
H-Index - 90
eISSN - 1552-4930
pISSN - 1552-4922
DOI - 10.1002/cyto.a.22108
Subject(s) - nijmegen breakage syndrome , biology , immunology , lymphocyte , b cell , population , immune system , antibody , immunoglobulin class switching , flow cytometry , memory b cell , recombination activating gene , humoral immunity , immunodeficiency , microbiology and biotechnology , genetics , gene , dna , medicine , dna damage , ataxia telangiectasia , recombination , environmental health
Patients with an immunodeficiency in the course of Nijmegen breakage syndrome (NBS) that is caused by mutations in the NBN / NBS1 gene are prone to recurrent infections and malignancies, due to a defective DNA double‐strand breaks repair mechanism. Four‐color flow cytometry was used to analyze changes in B lymphocyte subsets reflecting the most important stages of peripheral B cell maturation. It was demonstrated that the humoral immune defect observed in NBS patients was caused by reduced numbers of B lymphocytes, but also by their aberrant maturation. Reduced relative and absolute counts of naïve and memory B cells were accompanied by a significant accumulation of the natural effector B lymphocytes. The elevated proportion of IgM‐only memory and reduced proportion of IgM‐negative cells within the memory B cell pool suggests that there is class‐switch recombination defect in this population of cells in NBS patients, resulting in inadequate production of immunoglobulins. Because of the reduced T‐cell counts, the T‐cell dependent antigen response is severely impaired resulting in a lower frequency of memory B‐cells. The T‐cell independent B‐cell differentiation pathway seems less affected. The reduced IgG and IgA levels in patients with NBS are caused both by ineffective class switch, at least due to poor T cell help, and low number of memory B cells. This study illustrates that the NBN gene product nibrin plays an important role at different levels in the B‐cell system. © 2012 International Society for Advancement of Cytometry