Soluble CD14 enriched in colostrum and milk induces B cell growth and differentiation

Induction of resting B cell growth and differentiation requires a complex s eries of temporally coordinated signals that are initiated on contact with activated helper T cells. These signals complement one another, each render ing the B cell susceptible to factors supporting progressive activation. He re, we demonstrate that soluble CD14 (sCD14) bypasses the physiological seq uelae of events that limit B cell activation, a cell growth and differentia tion in vitro is induced by both native and recombinant forms of sCD14 at n anomolar concentrations. sCD14-mediated cellular activation does not requir e membrane CD14 expression, depends on a region of CD14 that is not involve d in lipopolysaccharide binding, and requires functional Toll-like receptor 4. Consistent with biological activity of sCD14 in vitro, its administrati on to neonatal mice enhances Ig secretion. The results presented establish sCD14 as a naturally occurring soluble B cell mitogen of mammalian origin.