An age-related numerical and functional deficit in CD19(+) CD24(hi) CD38(hi) B cells is associated with an increase in systemic autoimmunity.
Bottom Line: We found the frequency and numbers of CD19(+) CD24(hi) CD38(hi) cells were reduced in the PBMC pool with age.When investigating the mechanisms involved, we found that CD19(+) CD24(hi) CD38(hi) B-cell function was compromised by age-related effects on both T cells and B cells: specifically, CD40 ligand expression was lower in CD4 T cells from older donors following CD3 stimulation, and signalling through CD40 was impaired in CD19(+) CD24(hi) CD38(hi) B cells from elders as evidenced by reduced phosphorylation (Y705) and activation of STAT3.Finally, we found a negative correlation between CD19(+) CD24(hi) CD38(hi) B-cell IL10 production and autoantibody (Rheumatoid factor) levels in older adults.
Affiliation: MRC-ARUK Centre for Musculoskeletal Ageing Research, School of Immunity and Infection, Birmingham University Medical School, Birmingham, B15 2TT, UK.Show MeSH
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Mentions: The incidence of autoimmunity increases with age (Lindstrom & Robinson, 2010). For example, approximately 25% of older adults have detectable levels of low-affinity autoantibodies in their blood, including rheumatoid factors (RFs), which are present in only 5% of young healthy individuals (Moulias et al., 1984). Here, we have shown a numerical and functional impairment in the subset of IL10-producing B cells with age, and we thus questioned whether this impairment may contribute towards increased risk of autoimmunity with age. On testing serum RF levels of healthy young and aged individuals, we observed a significant increase in serum RF levels in older adults compared with young adults (Fig. 5A) and a significant negative correlation between RF antibody titre levels and IL10 production by CD19+CD24hiCD38hi B cells (P = 0.015; Fig. 5B). These results suggest that age -associated impairment in the ability of CD19+CD24hiCD38hi B cells to produce IL10 with age may be linked with the elevated risk of autoimmunity with age.
Affiliation: MRC-ARUK Centre for Musculoskeletal Ageing Research, School of Immunity and Infection, Birmingham University Medical School, Birmingham, B15 2TT, UK.