Abstract
BackgroundAge‐related immune deficiencies are thought to be responsible for increased susceptibility to infection in older adults, with alterations in lymphocyte populations becoming more prevalent over time. The loss of humoral immunity in ageing was attributed to the diminished numbers of B cells and the reduced ability to generate immunoglobulin.AimsTo compare the intrinsic B‐cell capacity for differentiation into mature plasma cells (PCs), between young and old donors, using in vitro assays, providing either effective T‐cell help or activation via TLR engagement.MethodsB cells were isolated from healthy individuals, in younger (30–38 years) and older (60–64 years) donors. An in vitro model system of B‐cell differentiation was used, analysing 5 differentiation markers by flow cytometry, under T‐dependent (TD: CD40/BCR stimulation) or T‐independent (TI: TLR7/BCR activation) conditions. Antibody secretion was measured by ELISA and gene expression using qPCR.ResultsTI and TD differentiation resulted in effective proliferation of B cells followed by their differentiation into PC. B‐cell‐executed TI differentiation was faster, all differentiation marker and genes being expressed earlier than under TD differentiation (day 6), although generating less viable cells and lower antibody levels (day 13). Age‐related differences in B‐cell capacity for differentiation were minimal in TD differentiation. In contrast, in TI differentiation age significantly affected proliferation, viability, differentiation, antibody secretion and gene expression, older donors being more efficient.ConclusionAltogether, B‐cell differentiation into PC appeared similar between age groups when provided with T‐cell help, in contrast to TI differentiation, where multiple age‐related changes suggest better capacities in older donors. These new findings may help explain the emergence of autoantibodies in ageing.
Highlights
There is no doubt that ageing is associated with multiple changes in different components of the immune system
Our data showed that TD differentiation and TI differentiation of B cells follow similar patterns in terms of phenotypic change and gene expression, it happened faster during TI, but generated more plasma cells (PCs) in TD
B-cell differentiation capacity appeared relatively similar between donors when using T-cell help, while some changes in overall PB and PC phenotype were observed in older donors
Summary
There is no doubt that ageing is associated with multiple changes in different components of the immune system. These assays can use a T-cell-dependent (TD) or T-cell-independent (TI) stimuli to activate the B cells and thereafter push them towards differentiation into EPB, a LPB and full PC status over 13 days These in vitro assays allow to compensate for any age-related factor that could affect the outcome, by providing controlled signals and environment to drive the generation of antibody-secreting PC. Both assays generate mature PC, with a phenotype and gene expression profile similar to ex vivo bone marrow-purified PC (Cocco et al, 2012). Generated PC numbers, their phenotype, secretary capability and gene expression profiles were compared
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