CD27- IgD- B cell memory subset associates with inflammation and frailty in elderly individuals but only in males

Abstract

Background Immunosenescence, i.e. the aging-associated decline of the capacity of the immune system, is characterized by several distinct changes in the number and functions of the immune cells. In the case of B cells, the total number of CD19+ B cells is lower in the blood of elderly individuals than in the younger ones. CD19+ B cell population contains several subsets, which are commonly characterized by the presence of CD27 and IgD molecules, i.e. naïve B cells (CD27- IgD+), IgM memory (CD27+ IgD+), switched memory (CD27+ IgD-) and late memory (CD27- IgD-). This late memory, double negative, population represents cells which are nondividing, but are still able to produce inflammatory mediators and in this way maybe contributing to the aging-associated inflammation, inflammaging. Here we have focused on the role of these B cell subsets in elderly individuals, nonagenarians, in the regulation of inflammation and inflammation-associated decline of bodily functions. As the biological aging process demonstrates gender-specific characteristics, the analyses were performed separately in males and female. Results A subcohort of The Vitality 90+ study (67 nonagenarians, 22/45 males/females and 40 young controls, 13/27 males/females) was used. Flow cytometric analysis indicated that the total percentage of the CD19+ cells was ca. 50% lower in the nonagenarians than in the controls in both genders. The proportions of these four B cell subsets within the CD19+ populations were very similar in young and old individuals. Thus, it seems that the aging-associated decline of the total CD19+ cells affects similarly all these B cell subsets. To analyze the role of these subsets in the regulation of inflammation, the correlation with IL-6 levels was calculated. A significant correlation was observed only with the percentage of CD27- IgD- cells and only in males. As inflammation is associated with aging-associated functional performance and frailty, the correlations with the Barthel index and frailty score was analyzed. Again, only the CD27- IgD- population demonstrated a strong male-specific correlation. Conclusions These data show that the CD27- IgD- B cell subset demonstrates a strong pro-inflammatory effect in nonagenarians, which significantly associates with the decline of the bodily functions. However, this phenomenon is only observed in males.

Influence of obesity on serum levels of SARS-CoV-2-specific antibodies in COVID-19 patients

“…Frequencies of DN B cells also increase in the blood of individuals with inflammatory conditions and diseases. These include aging [ 65 – 67 ], autoimmune diseases such as Systemic Lupus Erythematosus [ 68 – 70 ], Rheumatoid Arthritis [ 71 ], Sjogren’s disease [ 72 ], Multiple Sclerosis [ 73 ], Alzheimer’s disease [ 74 ], and pemphigus [ 75 ]. An increase of DN B cells has also been reported in the blood of COVID-19 patients and is associated with anti-viral antibody responses and poor clinical outcomes, as recently shown [ 76 ].…”

“…Frequencies of DN B cells also increase in the blood of individuals with inflammatory conditions and diseases. These include aging [65][66][67], autoimmune diseases Fig 1). �� p<0.01, ��� p<0.001.…”

Type I IFN-dependent antibody response at the basis of sex dimorphism in the outcome of COVID-19

“…Late memory B cells highly contributes to inflammaging as they express a senescence-associated secretory phenotype (SAPS), characterized by nondividing, metabolically active and secreting proinflammatory cytokines features [ 83 ]. Noteworthy, the increase of CD27-IgD- B cells in elderly males correlates with higher level of serum IL-6 only with respect to females [ 84 ]. Of interest, the inflammatory B-cell trait occurs together with a decline of IL-10 producing Breg cells, a condition associated with the production of autoantibodies in these subjects [ 85 ].…”

Phenotypic and Functional Characterization of Double Negative B Cells in the Blood of Individuals With Obesity

“…The reduced B cell resposes in individuals with obesity are likely due to the fact that B cells from obese individuals, as compared to those from lean individuals, are enriched in memory B cells, and in particular in the subset of Double Negative (DN) B cells, which is the most pro-inflammatory B cell subset (10,15), reported to be increased in the blood of individuals with inflammatory conditions and diseases. These include aging (16)(17)(18), autoimmune diseases such as Rheumatoid Arthritis (19), Systemic Lupus Erythematosus (SLE) (20,21), Multiple Sclerosis (22), Alzheimer's disease (23), Sjogren's disease (24) and pemphigus (25). DN B cells have also been reported to be increased in the blood of patients affected by chronic infectious diseases such as HIV (26), Hepatitis C (27) and Malaria (28).…”