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

• Autoři: MUGGEN A.F.; DE JONG M.; WOLVERS-TETTERO I.L.M.; KALLEMEIJN M.J.; TEODOSIO C.; DARZENTAS Nikos; 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.
• Rok publikování: 2019
• Druh: Článek v odborném periodiku
• Časopis / Zdroj: IMMUNITY & AGEING
• Fakulta / Pracoviště MU: Středoevropský technologický institut
• www: https://immunityageing.biomedcentral.com/track/pdf/10.1186/s12979-019-0163-x
• Doi: http://dx.doi.org/10.1186/s12979-019-0163-x
• Klíčová slova: Aging; B-lymphocyte; BCR repertoire; CLL; Stereotypic BCR
• Popis: 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.

Související projekty

• Encyklopedie CLL podskupin: unikátní znalostní databáze vybavená bioinformatickými nástroji použitelná v personalizované biomedicíně a klinické praxi