The presence of CLL-associated stereotypic B cell receptors in the normal BCR repertoire from healthy individuals increases with age
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 nonswitched 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.
|Keywords||Aging, B-lymphocyte, BCR repertoire, CLL, Stereotypic BCR|
|Persistent URL||dx.doi.org/10.1186/s12979-019-0163-x, hdl.handle.net/1765/121186|
|Journal||Immunity and Ageing|
Muggen, A.F, de Jong, M, Wolvers-Tettero, I.L.M, Kallemeijn, M.J, Teodosio, C, Darzentas, N, … Langerak, A.W. (2019). The presence of CLL-associated stereotypic B cell receptors in the normal BCR repertoire from healthy individuals increases with age. Immunity and Ageing, 16(1). doi:10.1186/s12979-019-0163-x