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

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. Electronic supplementary material The online version of this article (10.1186/s12979-019-0163-x) contains supplementary material, which is available to authorized users.

Establishing immune scoring model based on combination of the number, function, and phenotype of lymphocytes

“…In accordance with previous studies, our results demonstrated that the number of both T cells (including CD4 + and CD8 + T cells) and B cells gradually decreased with increasing age [12,13]. Previous studies have also shown that the diversity of B cell phenotype is decreased in elderly people, which results in decreased protective effect of vaccination in them compared with young people [12,[14][15][16]. These data suggest that the number of adaptive immune cells gradually decreases during life.…”

Overall reduced lymphocyte especially T and B subsets closely related to the poor prognosis and the disease severity in severe patients with COVID-19 and diabetes mellitus

“…It was found that the relative frequency and total number of B cells will decrease with age. Plasma blasts, memory cells and transitional B cells are decreased in patients older than 70 years [28]. Lymphocytes and their subsets [including NK cells (CD56+), B cells (CD19+) and T cells (CD3+)] are mainly responsible for regulating host immunity.…”

Overall reduced lymphocyte subsets worsening disease severity and prognosis in COVID-19 severe cases with diabetes mellitus in Chengdu, China

“…[24]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. [25]Lymphocytes and subsets including T(CD3+) cell, B(CD19+) cell and NK(CD56+) cell are mainly responsible for host immune regulation, T cells play a dominant role in promoting or sustaining in ammatory processes through inducing proin ammatory cytokines production. [23,[26][27][28][29]Activated Th1 cells, one subtype of CD4+ effector T cell, could trigger phagocyte-Previous research found that in COVID-19 patients higher expression of proin ammatory cytokines and chemokines, especially in the severe cases, the consumption of CD4+ and CD8+ T cells, and the decrease of regulatory T cells, might result in aggravated in ammatory responses, the production of cytokine storm and make damaged tissue worse.…”