Immunity & Ageing (Aug 2019)

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

  • Alice F. Muggen,
  • Madelon de Jong,
  • Ingrid L. M. Wolvers-Tettero,
  • Martine J. Kallemeijn,
  • Cristina Teodósio,
  • Nikos Darzentas,
  • Ralph Stadhouders,
  • Hanna IJspeert,
  • Mirjam van der Burg,
  • Wilfred FJ 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

DOI
https://doi.org/10.1186/s12979-019-0163-x
Journal volume & issue
Vol. 16, no. 1
pp. 1 – 12

Abstract

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Abstract 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.

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