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

• Published in: Aging cell Vol. 21; no. 9; pp. e13692 - n/a
• Main Authors: Lee, Jia Le, Fra‐Bido, Sigrid C., Burton, Alice R., Innocentin, Silvia, Hill, Danika L., Linterman, Michelle A.
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.09.2022; John Wiley and Sons Inc
• 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; ageing; antibodies; B cells; vaccine response
• ISSN: 1474-9718; 1474-9726
• DOI: 10.1111/acel.13692

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.