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.
Highlights
We found that the percentage of total CD19+ B cells as a fraction of total lymphocytes significantly decreased with advancing age (Figure 1A and Supplementary Figure 2A), consistent with previous reports [48,49,50,51,52]
We found the fraction of B-1 cells in the total CD19+ B cell population significantly declined with increasing age (Figure 1B)
B-1 cell percentages were compared grouping samples from donors within different age ranges. This analysis confirms a decrease in B-1 cell frequency with aging, which starts to be significant after the age of 50 (Supplementary Figure 2B)
Summary
Age-related diseases such as atherosclerosis, cancer, autoimmunity, type-2 diabetes mellitus, and microbial infection still have an impact on morbidity and mortality of elderly adults. Aging is accompanied by broad structural and functional changes in the immune system, usually related to increased susceptibility to the aforementioned diseases [1] and to decreased response to vaccination [2, 3]. There are two primary branches within the B cell population: conventional B-2 cells and B-1 cells. B-1 and B-2 cells differ in function and development, with B-2 cells originating mainly from the bone marrow and B-1 cells mainly from fetal liver and to a lesser extent from adult bone marrow [5, 6]. Conventional B-2 cells cooperate with T cells in the germinal center to provide high-affinity long lasting antibody
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