The presence of CLL-associated stereotypic B cell receptors in the normal BCR repertoire from healthy individuals increases with age.

Autor: Muggen AF; 1Department Immunology, Laboratory Medical Immunology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands., de Jong M; 1Department Immunology, Laboratory Medical Immunology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands., Wolvers-Tettero ILM; 1Department Immunology, Laboratory Medical Immunology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands., Kallemeijn MJ; 1Department Immunology, Laboratory Medical Immunology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands., Teodósio C; 1Department Immunology, Laboratory Medical Immunology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.; 2Present Address: Department Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands., Darzentas N; 3Central European Institute of Technology, Masaryk University, Brno, Czech Republic.; 4Department Internal Medicine, University Schleswig-Holstein, Kiel, Germany., Stadhouders R; 5Department Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands., IJspeert H; 1Department Immunology, Laboratory Medical Immunology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands., van der Burg M; 1Department Immunology, Laboratory Medical Immunology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.; 6Present Address: Department Pediatrics, Leiden University Medical Center, Leiden, The Netherlands., van IJcken WF; 7Biomics Core Facility, Erasmus MC, Rotterdam, The Netherlands., Verhaar JAN; 8Department Orthopedics, Erasmus MC, Rotterdam, The Netherlands., Abdulahad WH; 9Department Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands., Brouwer E; 9Department Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands., Boots AMH; 9Department Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands., Hendriks RW; 5Department Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands., van Dongen JJM; 1Department Immunology, Laboratory Medical Immunology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.; 2Present Address: Department Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands., Langerak AW; 1Department Immunology, Laboratory Medical Immunology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Immunity & ageing : I & A [Immun Ageing] 2019 Aug 28; Vol. 16, pp. 22. Date of Electronic Publication: 2019 Aug 28 (Print Publication: 2019).
DOI: 10.1186/s12979-019-0163-x
Abstrakt: Background: Aging is known to induce immunosenescence, resulting in alterations in both the innate and adaptive immune system. Here we evaluated the effects of aging on B cell subsets in peripheral blood of 155 immunologically healthy individuals in four age categories (range 20-95y) via multi-parameter flow cytometry. Furthermore, we studied the naive and antigen-experienced B cell receptor (BCR) repertoire of different age groups and compared it to the clonal BCR repertoire of chronic lymphocytic leukemia (CLL), a disease typically presenting in elderly individuals.
Results: Total numbers and relative frequencies of B cells were found to decline upon aging, with reductions in transitional B cells, memory cell types, and plasma blasts in the 70 + y group. The BCR repertoire of naive mature B cells and antigen-experienced B cells did not clearly alter until age 70y. Clear changes in IGHV gene usage were observed in naive mature B cells of 70 + y individuals, with a transitional pattern in the 50-70y group. IGHV gene usage of naive mature B cells of the 50-70y, but not the 70 + y, age group resembled that of both younger (50-70y) and older (70 + y) CLL patients. Additionally, CLL-associated stereotypic BCR were found as part of the healthy control BCR repertoire, with an age-associated increase in frequency of several stereotypic BCR (particularly subsets #2 and #5).
Conclusion: Composition of the peripheral B cell compartment changes with ageing, with clear reductions in non-switched and CD27 + IgG+ switched memory B cells and plasma blasts in especially the 70 + y group. The BCR repertoire is relatively stable until 70y, whereafter differences in IGHV gene usage are seen. Upon ageing, an increasing trend in the occurrence of particular CLL-associated stereotypic BCR is observed.
Competing Interests: Competing interestsThe authors declare that they have no competing interests.
Databáze: MEDLINE
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