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

Front Immunol. 2019 Mar 19;10:483. doi: 10.3389/fimmu.2019.00483. eCollection 2019.

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.

Keywords: IgM; aging; antibody secretion; human B-1 cells; repertoire.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / immunology*
  • Antibodies / immunology*
  • Antigens, CD / immunology
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocytes / immunology*
  • Cells, Cultured
  • Female
  • Humans
  • Immunoglobulin M / immunology
  • Immunologic Memory / immunology
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Positive Regulatory Domain I-Binding Factor 1 / immunology
  • Quality of Life
  • X-Box Binding Protein 1 / immunology
  • Young Adult

Substances

  • Antibodies
  • Antigens, CD
  • Immunoglobulin M
  • X-Box Binding Protein 1
  • Positive Regulatory Domain I-Binding Factor 1