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

Muggen, A. F., de Jong, M., Wolvers-Tettero, I. L. M., Kallemeijn, M. J., Teodosio, C., Darzentas, N., Stadhouders, R., Ijspeert, H., van der Burg, M., van Ijcken, W. F. J., Verhaar, J. A. N., Abdulahad, W. H., Brouwer, E., Boots, A. M. H., Hendriks, R. W., van Dongen, J. J. M. & Langerak, A. W., 28-Aug-2019, In : Immunity & ageing : I & A. 16, 1, 12 p., 22.

Research output: Contribution to journalArticleAcademicpeer-review

  • Alice F. Muggen
  • Madelon de Jong
  • Ingrid L. M. Wolvers-Tettero
  • Martine J. Kallemeijn
  • Cristina Teodosio
  • Nikos Darzentas
  • Ralph Stadhouders
  • Hanna Ijspeert
  • Mirjam van der Burg
  • Wilfred F. J. van Ijcken
  • Jan A. N. Verhaar
  • Wayel H. Abdulahad
  • Elisabeth Brouwer
  • Annemieke M. H. Boots
  • Rudi W. Hendriks
  • Jacques J. M. van Dongen
  • Anton W. Langerak

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.

Original languageEnglish
Article number22
Number of pages12
JournalImmunity & ageing : I & A
Issue number1
Publication statusPublished - 28-Aug-2019



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