Pearl knotting with silk is by far the oldest method to string the pearls to form a necklace. With silk thread, you must knot the silk between each bead. The reason for these knots is that the silk thread is softer than the pearls, and will not damage the delicate necre. But the pearl beads will slowly but surely saw their way through the silk, causing the necklace to break. With the knotting, in the worst case, you will only lose one bead when the strand breaks. And it is for that reason that pearl necklaces be restrung every two years.
With the introduction of modern beading threads onto the market. Freshwater pearls can now be strung as necklaces or bracelets on beading thread. The beading thread must be flexible yet strong or it will suffer metal fatigue and break. The only brand that is recommended for stringing pearls is the Soft Flex Brand. The .019 size Soft Touch, which is a premium Soft Flex product. With freshwater pearl beads you will find that the .014 or even .010 size of Soft Touch will be required due to the small size of the holes drilled in freshwater pearl beads.
Now that there is a bead stringing product that will not break, this means that tying knots between each bead is now unnecessary. So when using Soft Flex, a knot is not necessary between each pearl bead. You merely string the beads, you can put a seed bead, crystal or other bead between them; the only consideration being that you need a good tension on your beading thread, this way there will be less movement between the components resulting in less wear on your pearls/components.