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

• Main Authors: 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
• Format: Article
• Language: English
• Published: BMC 2019-08-01
• Series: Immunity & Ageing
• Subjects: Aging; B-lymphocyte; BCR repertoire; CLL; Stereotypic BCR
• Online Access: http://link.springer.com/article/10.1186/s12979-019-0163-x

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.