The advancing age affects the frequency, functions and antibody repertoire of human B-1 cells, which secrete anti-tumor antibodies

Aging decreases the efficiency of several physiological processes, including immune function, which has been associated with an increased incidence of infections, autoimmune diseases and cancer. Human B cell populations, like naive and memory B cells, suffer significant quantitative and qualitative changes in the elderly. The frequency and function of human B-1 cells, which play critical housekeeping and anti-microbial defensive roles, have not been studied. In the present work we analyzed how the frequency and function of human B-1 cells (CD20 + CD27 + CD43 + CD38 low ) change with age. Our results show that not only the percentage of B-1 cells but also their capacity to spontaneously secrete IgM decreased with age. In fact, expression levels of Xbp1 and Blimp1, associated with a secreting B cell phenotype, were significantly lower, while those of Pax5, characteristic of non-secreting B cells, were significantly higher in elderly donors. Since aging affects the humoral immune response both quantitatively and qualitatively, next we studied the antibody repertoire of B-1 cells of healthy young and elderly donors. Elderly donors showed a higher number of repeated clones and therefore, a reduction of the antibody repertoire variability in comparison with young individuals. Furthermore it was interesting to observe in aged individuals an increased frequency of VH3-23 and VH4-34 usage, genes which have been linked to autoimmune diseases and hematopoietic malignancies. Moreover, there is a significant reduction in older individuals of clones expressing the sequence VH3-33, frequently found on antibodies against PC, oxidized LDL, apoptotic cells and induced after vaccination with Pneumavax23.