Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations
(2023) In Cell Reports 42(5). p.1-19- Abstract
Common variable immune deficiency (CVID) is a heterogeneous disorder characterized by recurrent infections, low levels of serum immunoglobulins, and impaired vaccine responses. Autoimmune manifestations are common, but B cell central and peripheral selection mechanisms in CVID are incompletely understood. Here, we find that receptor editing, a measure of central tolerance, is increased in transitional B cells from CVID patients and that these cells have a higher immunoglobulin κ:λ ratio in CVID patients with autoimmune manifestations than in those with infection only. Contrariwise, the selection pressure in the germinal center on CD27
bright memory B cells is decreased in CVID patients with autoimmune manifestations. Finally,... (More)Common variable immune deficiency (CVID) is a heterogeneous disorder characterized by recurrent infections, low levels of serum immunoglobulins, and impaired vaccine responses. Autoimmune manifestations are common, but B cell central and peripheral selection mechanisms in CVID are incompletely understood. Here, we find that receptor editing, a measure of central tolerance, is increased in transitional B cells from CVID patients and that these cells have a higher immunoglobulin κ:λ ratio in CVID patients with autoimmune manifestations than in those with infection only. Contrariwise, the selection pressure in the germinal center on CD27
(Less)
bright memory B cells is decreased in CVID patients with autoimmune manifestations. Finally, functionally, T cell-dependent activation showed that naive B cells in CVID patients are badly equipped for activation and induction of mismatch repair genes. We conclude that central tolerance is functional whereas peripheral selection is defective in CVID patients with autoimmune manifestations, which could underpin the development of autoimmunity.
- author
- publishing date
- 2023-05-30
- type
- Contribution to journal
- publication status
- published
- keywords
- Humans, Common Variable Immunodeficiency/genetics, B-Lymphocytes, Germinal Center, Precursor Cells, B-Lymphoid, Autoimmunity
- in
- Cell Reports
- volume
- 42
- issue
- 5
- article number
- 112446
- pages
- 1 - 19
- publisher
- Cell Press
- external identifiers
-
- scopus:85153595326
- pmid:37119135
- ISSN
- 2211-1247
- DOI
- 10.1016/j.celrep.2023.112446
- language
- English
- LU publication?
- no
- additional info
- Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
- id
- 79d4b306-5c2b-46ac-ae29-cfc3b559cc52
- date added to LUP
- 2023-11-16 12:31:34
- date last changed
- 2024-04-14 16:58:37
@article{79d4b306-5c2b-46ac-ae29-cfc3b559cc52, abstract = {{<p>Common variable immune deficiency (CVID) is a heterogeneous disorder characterized by recurrent infections, low levels of serum immunoglobulins, and impaired vaccine responses. Autoimmune manifestations are common, but B cell central and peripheral selection mechanisms in CVID are incompletely understood. Here, we find that receptor editing, a measure of central tolerance, is increased in transitional B cells from CVID patients and that these cells have a higher immunoglobulin κ:λ ratio in CVID patients with autoimmune manifestations than in those with infection only. Contrariwise, the selection pressure in the germinal center on CD27 <br> bright memory B cells is decreased in CVID patients with autoimmune manifestations. Finally, functionally, T cell-dependent activation showed that naive B cells in CVID patients are badly equipped for activation and induction of mismatch repair genes. We conclude that central tolerance is functional whereas peripheral selection is defective in CVID patients with autoimmune manifestations, which could underpin the development of autoimmunity.<br> </p>}}, author = {{Friman, Vanda and Quinti, Isabella and Davydov, Alexey N and Shugay, Mikhail and Farroni, Chiara and Engström, Erik and Pour Akaber, Shirin and Barresi, Sabina and Mohamed, Ahmed and Pulvirenti, Federica and Milito, Cinzia and Granata, Guido and Giorda, Ezio and Ahlström, Sara and Karlsson, Johanna and Marasco, Emiliano and Marcellini, Valentina and Bocci, Chiara and Cascioli, Simona and Scarsella, Marco and Phad, Ganesh and Tilevik, Andreas and Tartaglia, Marco and Bemark, Mats and Chudakov, Dmitriy M and Carsetti, Rita and Grimsholm, Ola}}, issn = {{2211-1247}}, keywords = {{Humans; Common Variable Immunodeficiency/genetics; B-Lymphocytes; Germinal Center; Precursor Cells, B-Lymphoid; Autoimmunity}}, language = {{eng}}, month = {{05}}, number = {{5}}, pages = {{1--19}}, publisher = {{Cell Press}}, series = {{Cell Reports}}, title = {{Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations}}, url = {{http://dx.doi.org/10.1016/j.celrep.2023.112446}}, doi = {{10.1016/j.celrep.2023.112446}}, volume = {{42}}, year = {{2023}}, }