B cell‐intrinsic changes with age do not impact antibody‐secreting cell formation but delay B cell participation in the germinal centre reaction

Vaccines typically protect against (re)infections by generating pathogen‐neutralising antibodies. However, as we age, antibody‐secreting cell formation and vaccine‐induced antibody titres are reduced. Antibody‐secreting plasma cells differentiate from B cells either early post‐vaccination through th...

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Bibliographic Details
Published in:Aging cell 2022-09, Vol.21 (9), p.e13692-n/a
Main Authors: Lee, Jia Le, Fra‐Bido, Sigrid C., Burton, Alice R., Innocentin, Silvia, Hill, Danika L., Linterman, Michelle A.
Format: Article
Language:English
Subjects:
Adoptive transfer
Age
ageing
Aging
Animals
Antibodies
Antibody Formation
Antibody response
Antibody-Producing Cells
Antigens
B cells
B-Lymphocytes
Cell differentiation
Cell proliferation
Defects
Dendritic cells
Germinal Center
Germinal centers
Humans
Humoral immunity
Infections
Lymphocytes
Lymphocytes B
Mice
Older people
Plasma
Plasma Cells
vaccine response
Vaccines
Young adults
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Summary:Vaccines typically protect against (re)infections by generating pathogen‐neutralising antibodies. However, as we age, antibody‐secreting cell formation and vaccine‐induced antibody titres are reduced. Antibody‐secreting plasma cells differentiate from B cells either early post‐vaccination through the extrafollicular response or from the germinal centre (GC) reaction, which generates long‐lived antibody‐secreting cells. As the formation of both the extrafollicular antibody response and the GC requires the interaction of multiple cell types, the impaired antibody response in ageing could be caused by B cell intrinsic or extrinsic factors, or a combination of the two. Here, we show that B cells from older people do not have intrinsic defects in their proliferation and differentiation into antibody‐secreting cells in vitro compared to those from the younger donors. However, adoptive transfer of B cells from aged mice to young recipient mice showed that differentiation into extrafollicular plasma cells was favoured at the expense of B cells entering the GC during the early stages of GC formation. In contrast, by the peak of the GC response, GC B cells derived from the donor cells of aged mice had expanded to the same extent as those from the younger donors. This indicates that age‐related intrinsic B cell changes delay the GC response but are not responsible for the impaired antibody‐secreting response or smaller peak GC response in ageing. Collectively, this study shows that B cells from aged individuals are not intrinsically defective in responding to stimulation and becoming antibody‐secreting cells, implicating B cell‐extrinsic factors as the primary cause of age‐associated impairment in the humoral immunity. The effects of cell‐intrinsic changes on B cells function during ageing remain unknown. Here, we found that B cells from older humans do not have defects in activation, proliferation and antibody‐secreting cell differentiation when stimulated in vitro. B cells from aged mice displayed a delay in germinal centre formation and preferential differentiation into extrafollicular plasma cells, compared to B cells from young mice early post‐immunisation, but mounted comparable germinal centre when the germinal centre response has matured.
ISSN:1474-9718
1474-9726
DOI:10.1111/acel.13692