[HTML][HTML] Human B-1 cells and B-1 cell antibodies change with advancing age

N Rodriguez-Zhurbenko, TD Quach… - Frontiers in …, 2019 - frontiersin.org
N Rodriguez-Zhurbenko, TD Quach, TJ Hopkins, TL Rothstein, AM Hernandez
Frontiers in immunology, 2019frontiersin.org
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+ CD38 low/int CD43+) …
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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