Human B-1 Cells and B-1 Cell Antibodies Change With Advancing Age

Abstract

Age-related deficits in the immune system have been associated with an increased incidence of infections, autoimmune diseases, and cancer. Human B cell populations change quantitatively and qualitatively in the elderly. However, the function of human B-1 cells, which play critical anti-microbial and housekeeping roles, have not been studied in the older age population. In the present work, we analyzed how the frequency, function and repertoire of human peripheral blood B-1 cells (CD19+CD20+CD27+CD38low/intCD43+) change with age. Our results show that not only the percentage of B-1 cells but also their ability to spontaneously secrete IgM decreased with age. Further, expression levels of the transcription factors XBP-1 and Blimp-1 were significantly lower, while PAX-5, characteristic of non-secreting B cells, was significantly higher, in healthy donors over 65 years (old) as compared to healthy donors between 20 and 45 years (young). To further characterize the B-1 cell population in older individuals, we performed single cell sequencing analysis of IgM heavy chains from healthy young and old donors. We found reduced repertoire diversity of IgM antibodies in B-1 cells from older donors as well as differences in usage of certain VH and DH specific genes, as compared to younger. Overall, our results show impairment of the human B-1 cell population with advancing age, which might impact the quality of life and onset of disease within the elderly population.

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“…[44][45][46] A more recent study also found a reduced diversity in natural IgM antibodies in older donors, 86 reflecting a similar trend observed in human B-1 B cells, the cells responsible for natural IgM production, mainly in the spleen. 87 This evidence may contribute to explain the increasing prevalence of severe cases of COVID-19 in the eldest. 44-46…”

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“…The antibody repertoire of B-1 cells from healthy old individuals differs from that of healthy young individuals in ways that restrict diversity. Beside a cell intrinsic defect in spontaneous immunoglobulin secretion, it was shown a reduction in IgM antibody heterogeneity among B-1 cells from old donors [46].…”

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“…This immune scenario of repertoire freeze (8) is supported by an analysis of the natural antibody repertoire in older individuals (40) : (1) the number of B1 cells is reduced, whereas nonsecreting B1 cells are increased. (2) the IgM repertoire in natural antibody repertoire is less diverse in the elderly than in younger people.…”