A Study of Serum Immunoglobulin Levels in Elderly Persons That Provides New Insights into B Cell Immunosenescence

Abstract

The literature on immunosenescence has focused mainly on T cell impairment. With the aim of gaining insight into B cell immunosenescence, we investigated the serum immunoglobulin levels in a cohort of 166 subjects (20-106 years). Serum IgG (and IgG subclasses) were quantified by the nephelometric technique, IgE by CAP system fluorescence enzyme immunoassay, and IgD by radial immunodiffusion (RID). There was an age-related increase of IgG and IgA; the IgG age-related increase was significant only in men, but IgG1 levels showed an age-related increase both in men and women, whereas IgG3 showed an age-related increase only in men. IgE levels remain unchanged, whereas IgD and IgM serum levels decreased with age; the IgM age-related decrease was significant only in women, likely due to the relatively small sample of aged men. Thus, in the elderly the B cell repertoire available to respond to new antigenic challenge is decreased. A lot of memory IgD- B cells are filling immunological space and the amount of naïve IgD+ B cells is dramatically decreased. This shift away from a population of predominantly naïve B cells obviously reflects the influences of cumulative exposure to foreign pathogens over time. These age-dependent B cell changes indicate that advanced age is a condition characterized by lack of clonotypic immune response to new extracellular pathogens. In any event, the increase of memory B cells and the loss of naïve B cells, as measured by serum IgD levels, could represent hallmarks of immunosenescence and could provide useful biomarkers possibly related to the life span of humans.

B Cells Compartment in Centenarian Offspring and Old People

“…In fact we have recently demonstrated an increase of late (exhausted) memory B cells in elderly [20] also accompanied by a decrease of serum IgM, so confirming the loss of naïve cells/products (i.e. antibodies) in the elderly [21]. Here we show that centenarian offspring have an increased amount of naïve B cells and IgM when compared to their controls, whereas we do not observe the increase of DN B cells shown in healthy elderly people.…”

Cytokine Serum Profile in a Group of Sicilian Nonagenarians

“…The decrement of virgin CD27 À B lymphocytes cells and the concurrent increase of memory CD27 þ B lymphocytes seem to have an impact on the antibody repertoire of older individuals. [19][20][21] In this view, our data might be related to the different role played by IL-4 and IL-13 in the Th2 switch and B cell response maintenance in aging. Actually the Th2 switch, where IL-4 has a major key role, is already strongly reduced in advanced aged individuals, where there is a higher ratio between differentiated memory cells and virgin naïve ones, whereas, IL13 is mainly produced by primed Th2 cells.…”

“…It is reported that advanced-aged individuals are characterized by high plasma levels of immunoglobulins. [19] In particular IgG, IgA, and IgE levels are increased. Analysis of Th2 cytokines shows similar IL-5 levels among nonagenarians and young controls.…”

B cell immunosenescence: different features of naive and memory B cells in elderly

“…This is in agreement with previous data that have demonstrated a reduction of IgM ''only'' memory B cells in the elderly (Shi et al 2005). We show a slight increase in the expression of IgG and IgA on switched memory B cells but this did not reach significance, although the relative proportions of the different isotypes of memory cells mirrors the relative proportion of serum immunoglobulin of the different isotypes (Paganelli et al 1992;Listì et al 2006).…”