Long-term kinetics of adult human antibody repertoires

Abstract

In healthy humans, antibody repertoires change during ontogeny and senescence. The dynamics of antibody repertoires among adults over a longer period of time in one and the same individual has, however, not been extensively studied. In this study we analysed peripheral blood samples from five healthy adults, taken over a period of 10 weeks and once 9 years later. A competitive, quantitative polymerase chain reaction (PCR) was developed to investigate short and long-term variations in VH gene family repertoires. Serum antibody levels to common self and non-self antigens were determined in samples taken at the same time-points as the cell samples to analyse possible correlations between molecular and serological expression profiles. We found a high degree of stability in the VH gene family repertoire over time as well as between individuals with a Caucasian background. A specific change in the usage of primarily the VH3 and VH5 gene families was observed in one individual at one time-point. The deviating pattern resembled the VH gene family utilization pattern observed in naturally activated B lymphocytes. The fluctuations in VH3 and VH5 gene family expression correlated with the presence of rheumatoid factor in serum. We discuss the possible influence of polyclonal, transient stimulation of B cells on VH gene repertoires, as measured in circulating B cells.